{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:22:36Z","timestamp":1790504556258,"version":"4.1.0"},"reference-count":259,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C14\/19\/095"],"award-info":[{"award-number":["C14\/19\/095"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0B4819N"],"award-info":[{"award-number":["G0B4819N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["W001420N"],"award-info":[{"award-number":["W001420N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006282","name":"Koning Boudewijnstichting","doi-asserted-by":"publisher","award":["2020-J1190990-215254"],"award-info":[{"award-number":["2020-J1190990-215254"]}],"id":[{"id":"10.13039\/501100006282","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone morphogenetic proteins (BMPs) were originally identified as the active components in bone extracts that can induce ectopic bone formation. In recent decades, their key role has broadly expanded beyond bone physiology and pathology. Nowadays, the BMP pathway is considered an important player in vascular signaling. Indeed, mutations in genes encoding different components of the BMP pathway cause various severe vascular diseases. Their signaling contributes to the morphological, functional and molecular heterogeneity among endothelial cells in different vessel types such as arteries, veins, lymphatic vessels and capillaries within different organs. The BMP pathway is a remarkably fine-tuned pathway. As a result, its signaling output in the vessel wall critically depends on the cellular context, which includes flow hemodynamics, interplay with other vascular signaling cascades and the interaction of endothelial cells with peri-endothelial cells and the surrounding matrix. In this review, the emerging role of BMP signaling in lymphatic vessel biology will be highlighted within the framework of BMP signaling in the circulatory vasculature.<\/jats:p>","DOI":"10.3390\/ijms22126364","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T10:30:25Z","timestamp":1623666625000},"page":"6364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0721-168X","authenticated-orcid":false,"given":"Ljuba C.","family":"Ponomarev","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (CMVB), KU Leuven, Herestraat 49 Box 911, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1060-2710","authenticated-orcid":false,"given":"Jakub","family":"Ksiazkiewicz","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (CMVB), KU Leuven, Herestraat 49 Box 911, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Staring","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (CMVB), KU Leuven, Herestraat 49 Box 911, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aernout","family":"Luttun","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (CMVB), KU Leuven, Herestraat 49 Box 911, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1721","authenticated-orcid":false,"given":"An","family":"Zwijsen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (CMVB), KU Leuven, Herestraat 49 Box 911, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Garc\u00eda de Vinuesa, A., Abdelilah-Seyfried, S., Knaus, P., Zwijsen, A., and Bailly, S. (2015). BMP signaling in vascular biology and dysfunction. Cytokine Growth Factor Rev.","DOI":"10.1016\/j.cytogfr.2015.12.005"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Goumans, M.-J., Zwijsen, A., ten Dijke, P., and Bailly, S. (2018). Bone morphogenetic proteins in vascular homeostasis and disease. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a031989"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrcardio.2015.156","article-title":"Targeting BMP signalling in cardiovascular disease and anaemia","volume":"13","author":"Morrell","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1161\/CIRCRESAHA.117.309930","article-title":"Deregulated TGF-\u03b2\/BMP signaling in vascular malformations","volume":"121","author":"Cunha","year":"2017","journal-title":"Circ. Res."},{"key":"ref_5","first-page":"893","article-title":"Bone: Formation by autoinduction","volume":"150","author":"Urist","year":"1965","journal-title":"New Ser."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1177\/00220345710500060601","article-title":"Bone morphogenetic protein","volume":"50","author":"Urist","year":"1971","journal-title":"J. Dent. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sampath, T.K., and Reddi, A.H. (2020). Discovery of bone morphogenetic proteins\u2014A historical perspective. Bone, 140.","DOI":"10.1016\/j.bone.2020.115548"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gendis.2014.07.005","article-title":"Bone Morphogenetic Protein (BMP) signaling in development and human diseases","volume":"1","author":"Wang","year":"2014","journal-title":"Genes Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Derynck, R., and Budi, E.H. (2019). Specificity, versatility, and control of TGF-b family signaling. Sci. Signal., 12.","DOI":"10.1126\/scisignal.aav5183"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/bs.ctdb.2019.10.012","article-title":"Temporal dynamics in the formation and interpretation of Nodal and BMP morphogen gradients","volume":"137","author":"Economou","year":"2020","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S1359-6101(99)00025-8","article-title":"TGF-\u03b2 signaling by Smad proteins","volume":"11","author":"Miyazono","year":"2000","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-1-4939-2966-5_4","article-title":"Production, isolation, and structural analysis of ligands and receptors of the TGF-\u03b2 superfamily","volume":"1344","author":"Huang","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1093\/emboj\/21.7.1743","article-title":"Balancing the activation state of the endothelium via two distinct TGF-\u03b2 type I receptors","volume":"21","author":"Goumans","year":"2002","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1182\/blood-2006-07-034124","article-title":"Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells","volume":"109","author":"David","year":"2007","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1096\/fj.201700193RR","article-title":"Role of bone morphogenetic proteins in sprouting angiogenesis: Differential BMP receptor-dependent signaling pathways balance stalk vs. tip cell competence","volume":"31","author":"Benn","year":"2017","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.febslet.2012.02.043","article-title":"Promiscuity and specificity in BMP receptor activation","volume":"586","author":"Mueller","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5330","DOI":"10.1074\/jbc.M102750200","article-title":"The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways","volume":"277","author":"Nohe","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1091\/mbc.11.3.1023","article-title":"Bone morphogenetic protein receptor complexes on the surface of live cells: A new oligomerization mode for serine\/threonine kinase receptors","volume":"11","author":"Gilboa","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1016\/j.cellsig.2011.04.004","article-title":"Homomeric and heteromeric complexes among TGF-\u0392 and BMP receptors and their roles in signaling","volume":"23","author":"Ehrlich","year":"2011","journal-title":"Cell. Signal."},{"key":"ref_20","first-page":"1392","article-title":"Endoglin regulates the activation and quiescence of endothelium by participating in canonical and non-canonical TGF-\u03b2 signaling pathways","volume":"126","author":"Park","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.tcb.2016.11.009","article-title":"RGMs: Structural insights, molecular regulation, and downstream signaling","volume":"27","author":"Siebold","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1097-2765(01)00332-X","article-title":"The TGF\u03b2 receptor activation process: An inhibitor- to substrate-binding switch","volume":"8","author":"Huse","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39492","DOI":"10.1074\/jbc.M112.387639","article-title":"SMAD versus non-SMAD signaling is determined by lateral mobility of bone morphogenetic protein (BMP) receptors","volume":"287","author":"Guzman","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hill, C.S. (2016). Transcriptional control by the SMADs. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a022079"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.semcdb.2014.01.009","article-title":"TGF-\u03b2 signaling to chromatin: How Smads regulate transcription during self-renewal and differentiation","volume":"32","author":"Gaarenstroom","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.molcel.2007.01.006","article-title":"Balancing BMP Signaling through Integrated Inputs into the Smad1 Linker","volume":"25","author":"Sapkota","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1111\/j.1440-1681.2011.05592.x","article-title":"Cell biology of Smad2\/3 linker region phosphorylation in vascular smooth muscle","volume":"39","author":"Rezaei","year":"2012","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4490","DOI":"10.1038\/sj.emboj.7601332","article-title":"Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription","volume":"25","author":"Ross","year":"2006","journal-title":"EMBO J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1164\/rccm.201106-1130OC","article-title":"Altered MicroRNA processing in heritable pulmonary arterial hypertension: An important role for Smad-8","volume":"184","author":"Drake","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1126\/science.1192149","article-title":"Noncanonical TGF\u03b2 signaling contributes to aortic aneurysm progression in marfan syndrome mice","volume":"332","author":"Holm","year":"2011","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hiepen, C., Mendez, P.-L., and Knaus, P. (2020). It takes two to tango: Endothelial TGF\u03b2\/BMP Signaling crosstalk with mechanobiology. Cells, 9.","DOI":"10.3390\/cells9091965"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1161\/CIRCRESAHA.114.302452","article-title":"Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos","volume":"114","author":"Dunworth","year":"2014","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1182\/blood-2012-12-472142","article-title":"Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation","volume":"122","author":"Levet","year":"2013","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18940","DOI":"10.1073\/pnas.1310479110","article-title":"Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression","volume":"110","author":"Yoshimatsu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.stemcr.2018.11.024","article-title":"Bone morphogenetic protein 9 regulates early lymphatic-specified endothelial cell expansion during mouse embryonic stem cell differentiation","volume":"12","author":"Subileau","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1182\/blood-2009-07-235655","article-title":"ALK1 signaling regulates early postnatal lymphatic vessel development","volume":"115","author":"Niessen","year":"2010","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"270","DOI":"10.14348\/molcells.2014.0005","article-title":"Alk3\/Alk3b and Smad5 mediate BMP signaling during lymphatic development in zebrafish","volume":"37","author":"Kim","year":"2014","journal-title":"Mol. Cells"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10456-020-09713-1","article-title":"TMEM100 is a key factor for specification of lymphatic endothelial progenitors","volume":"23","author":"Moon","year":"2020","journal-title":"Angiogenesis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1038\/sj.onc.1210182","article-title":"Functional implication of BMP4 expression on angiogenesis in malignant melanoma","volume":"26","author":"Rothhammer","year":"2007","journal-title":"Oncogene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1158\/1541-7786.141.2.3","article-title":"Bone Morphogenetic Protein-2 stimulates angiogenesis in developing tumors","volume":"2","author":"Langenfeld","year":"2004","journal-title":"Mol. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1242\/jcs.002949","article-title":"BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis","volume":"120","author":"Scharpfenecker","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/s41467-020-15425-3","article-title":"Molecular basis of ALK1-mediated signalling by BMP9\/BMP10 and their prodomain-bound forms","volume":"11","author":"Salmon","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1242\/dev.01094","article-title":"BMP10 is essential for maintaining cardiac growth during murine cardiogenesis","volume":"131","author":"Chen","year":"2004","journal-title":"Development"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1086\/316915","article-title":"Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome","volume":"67","author":"Fang","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11887","DOI":"10.1073\/pnas.1306074110","article-title":"Context-dependent signaling defines roles of BMP9 and BMP10 in embryonic and postnatal development","volume":"110","author":"Chen","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Xiang, M., Grosso, R.A., Takeda, A., Pan, J., Bekkhus, T., Brulois, K., Dermadi, D., Nordling, S., Vanlandewijck, M., and Jalkanen, S. (2020). A single-cell transcriptional roadmap of the mouse and human lymph node lymphatic vasculature. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.00052"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Moya, I.M., Umans, L., Maas, E., Pereira, P.G., Beets, K., Francis, A., Sents, W., Robertson, E.J., Mummery, C.L., and Huylebroeck, D. (2012). Stalk cell phenotype depends on integration of notch and Smad1\/5 signaling cascades. Dev. Cell, 22.","DOI":"10.1016\/j.devcel.2012.01.007"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1093\/hmg\/ddp214","article-title":"Defective pulmonary vascular remodeling in Smad8 mutant mice","volume":"18","author":"Huang","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1164\/rccm.201411-1985LE","article-title":"Endothelial chromosome 13 deletion in congenital heart disease-associated pulmonary arterial hypertension dysregulates SMAD9 signaling","volume":"191","author":"Drake","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wang, Z.P., Mu, X.Y., Guo, M., Wang, Y.J., Teng, Z., Mao, G.P., Niu, W.B., Feng, L.Z., Zhao, L.H., and Xia, G.L. (2014). Transforming growth factor-\u03b2 signaling participates in the maintenance of the primordial follicle pool in the mouse ovary. J. Biol. Chem.","DOI":"10.1074\/jbc.M113.532952"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1016\/j.bpj.2018.03.018","article-title":"Nuclear transport and accumulation of smad proteins studied by single-molecule microscopy","volume":"114","author":"Li","year":"2018","journal-title":"Biophys. J."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Richter, A., Alexdottir, M.S., Magnus, S.H., Richter, T.R., Morikawa, M., Zwijsen, A., and Valdimarsdottir, G. (2019). EGFL7 mediates BMP9-induced sprouting angiogenesis of endothelial cells derived from human embryonic stem cells. Stem Cell Rep.","DOI":"10.1016\/j.stemcr.2019.04.022"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Morikawa, M., Mitani, Y., Holmborn, K., Kato, T., Koinuma, D., Maruyama, J., Vasilaki, E., Sawada, H., Kobayashi, M., and Ozawa, T. (2019). The ALK-1\/SMAD\/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension. Sci. Signal., 12.","DOI":"10.1126\/scisignal.aay4430"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12064","DOI":"10.1073\/pnas.1207210109","article-title":"Tmem100, an ALK1 receptor signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis","volume":"109","author":"Somekawa","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1161\/01.CIR.0000033830.36431.46","article-title":"Stimulation of Id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells","volume":"106","author":"Valdimarsdottir","year":"2002","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/dvg.20402","article-title":"Real time monitoring of BMP smads transcriptional activity during mouse development","volume":"46","author":"Monteiro","year":"2008","journal-title":"Genesis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1242\/jcs.01337","article-title":"Spatio-temporal activation of Smad1 and Smad5 in vivo: Monitoring transcriptional activity of Smad proteins","volume":"117","author":"Monteiro","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/dvdy.22567","article-title":"Dynamic smad-mediated BMP signaling revealed through transgenic zebrafish","volume":"240","author":"Collery","year":"2011","journal-title":"Dev. Dyn."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Javier, A.L., Doan, L.T., Luong, M., Reyes de Mochel, N.S., Sun, A., Monuki, E.S., and Cho, K.W.Y. (2012). Bmp Indicator Mice Reveal Dynamic Regulation of Transcriptional Response. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042566"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/dvdy.22558","article-title":"Dynamic analysis of BMP-responsive smad activity in live zebrafish embryos","volume":"240","author":"Laux","year":"2011","journal-title":"Dev. Dyn."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/path.2844","article-title":"Direct visualization of Smad1\/5\/8-mediated transcriptional activity identifies podocytes and collecting ducts as major targets of BMP signalling in healthy and diseased kidneys","volume":"224","author":"Leeuwis","year":"2011","journal-title":"J. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Beets, K., Staring, M.W., Criem, N., Maas, E., Schellinx, N., de Sousa Lopes, S.M.C., Umans, L., and Zwijsen, A. (2016). BMP-SMAD signalling output is highly regionalized in cardiovascular and lymphatic endothelial networks. BMC Dev. Biol., 16.","DOI":"10.1186\/s12861-016-0133-x"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.semcdb.2014.01.008","article-title":"Regulation of TGF\u03b2 and related signals by precursor processing","volume":"32","author":"Constam","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3109\/08977194.2011.608666","article-title":"Prodomains regulate the synthesis, extracellular localisation and activity of TGF-\u03b2 superfamily ligands","volume":"29","author":"Harrison","year":"2011","journal-title":"Growth Factors"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1074\/jbc.M110.188615","article-title":"Prodomains of transforming growth factor \u03b2 (TGF\u03b2) Superfamily members specify different functions: Extracellular matrix interactions and growth factor bioavailability","volume":"286","author":"Sengle","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1083\/jcb.200312172","article-title":"Integrin \u03b1v\u03b26-mediated activation of latent TGF-\u03b2 requires the latent TGF-\u03b2 binding protein-1","volume":"165","author":"Annes","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature10152","article-title":"Latent TGF-\u03b2 structure and activation","volume":"474","author":"Shi","year":"2011","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Katagiri, T., and Watabe, T. (2016). Bone morphogenetic proteins. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a021899"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.jmb.2008.06.074","article-title":"A New Model for Growth Factor Activation: Type II Receptors Compete with the Prodomain for BMP-7","volume":"381","author":"Sengle","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3710","DOI":"10.1073\/pnas.1501303112","article-title":"Structure of bone morphogenetic protein 9 procomplex","volume":"112","author":"Mi","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.ceb.2009.05.005","article-title":"Extracellular microfibrils: Contextual platforms for TGF\u03b2 and BMP signaling","volume":"21","author":"Ramirez","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"13874","DOI":"10.1074\/jbc.M707820200","article-title":"Targeting of bone morphogenetic protein growth factor complexes to fibrillin","volume":"283","author":"Sengle","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.bbapap.2012.07.002","article-title":"Prediction of heparin binding sites in bone morphogenetic proteins (BMPs)","volume":"1824","author":"Gandhi","year":"2012","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7226","DOI":"10.1016\/j.biomaterials.2010.05.022","article-title":"The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis","volume":"31","author":"Choi","year":"2010","journal-title":"Biomaterials"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"De Laporte, L., Rice, J.J., Tortelli, F., and Hubbell, J.A. (2013). Tenascin C promiscuously binds growth factors via its fifth fibronectin type III-like domain. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062076"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.bbrc.2005.02.013","article-title":"Cyclic strain-mediated regulation of vascular endothelial cell migration and tube formation","volume":"329","author":"Cummins","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.cardiores.2004.05.008","article-title":"Cyclic strain-mediated regulation of endothelial matrix metalloproteinase-2 expression and activity","volume":"63","author":"Cummins","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/ncb1870","article-title":"Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis","volume":"11","author":"Little","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Tajer, B., Dutko, J.A., Little, S.C., and Mullins, M.C. (2021). BMP heterodimers signal via distinct type I receptor class functions. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2017952118"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kim, H.S., Neugebauer, J., McKnite, A., Tilak, A., and Christian, J.L. (2019). BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis. eLife, 8.","DOI":"10.7554\/eLife.48872"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1128\/MCB.02062-07","article-title":"Emilin1 deficiency causes structural and functional defects of lymphatic vasculature","volume":"28","author":"Danussi","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1083\/jcb.36.1.129","article-title":"Ultrastructural studies on the lymphatic anchoring filaments","volume":"36","author":"Leak","year":"1968","journal-title":"J. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/abbs\/gmx126","article-title":"TGF-\u03b2 family co-receptor function and signaling","volume":"50","author":"Nickel","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1074\/jbc.274.2.584","article-title":"Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-\u03b2 superfamily","volume":"274","author":"Barbara","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Schoonderwoerd, M.J.A., Goumans, M.J.T.H., and Hawinkels, L.J.A.C. (2020). Endoglin: Beyond the endothelium. Biomolecules, 10.","DOI":"10.3390\/biom10020289"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Alt, A., Miguel-Romero, L., Donderis, J., Aristorena, M., Blanco, F.J., Round, A., Rubio, V., Bernabeu, C., and Marina, A. (2012). Structural and functional insights into endoglin ligand recognition and binding. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029948"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1038\/emboj.2012.246","article-title":"Endoglin mediates fibronectin\/\u03b15\u03b21 integrin and TGF-\u03b2 pathway crosstalk in endothelial cells","volume":"31","author":"Tian","year":"2012","journal-title":"EMBO J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cytogfr.2009.10.007","article-title":"Recent advances in BMP receptor signaling","volume":"20","author":"Sieber","year":"2009","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7628","DOI":"10.1074\/jbc.M704883200","article-title":"Bone morphogenetic proteins signal through the transforming growth factor-\u03b2 type III receptor","volume":"283","author":"Kirkbride","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nsmb.3016","article-title":"Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein","volume":"22","author":"Healey","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Halbrooks, P.J., Ding, R., Wozney, J.M., and Bain, G. (2007). Role of RGM coreceptors in bone morphogenetic protein signaling. J. Mol. Signal., 2.","DOI":"10.1186\/1750-2187-2-4"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Gipson, G.R., Goebel, E.J., Hart, K.N., Kappes, E.C., Kattamuri, C., McCoy, J.C., and Thompson, T.B. (2020). Structural perspective of BMP ligands and signaling. Bone, 140.","DOI":"10.1016\/j.bone.2020.115549"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Aspalter, I.M., Gordon, E., Dubrac, A., Ragab, A., Narloch, J., Viz\u00e1n, P., Geudens, I., Collins, R.T., Franco, C.A., and Abrahams, C.L. (2015). Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch. Nat. Commun., 6.","DOI":"10.1038\/ncomms8264"},{"key":"ref_94","first-page":"4363","article-title":"Neuropilin 1 balances \u03b28 integrin-activated TGF\u03b2 signaling to control sprouting angiogenesis in the brain","volume":"142","author":"Hirota","year":"2015","journal-title":"Dev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/carcin\/bgq281","article-title":"Neuropilin-1 exerts co-receptor function for TGF-beta-1 on the membrane of cancer cells and enhances responses to both latent and active TGF-beta","volume":"32","author":"Glinka","year":"2011","journal-title":"Carcinogenesis"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1083\/jcb.200602080","article-title":"Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments","volume":"174","author":"Lampugnani","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/emboj.2008.46","article-title":"VE-cadherin is a critical endothelial regulator of TGF-\u03b2 signalling","volume":"27","author":"Rudini","year":"2008","journal-title":"EMBO J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1242\/jcs.179960","article-title":"VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling","volume":"129","author":"Benn","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Ouahoud, S., Hardwick, J.C.H., and Hawinkels, L.J.A.C. (2020). Extracellular bmp antagonists, multifaceted orchestrators in the tumor and its microenvironment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113888"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nature01245","article-title":"Structural basis of BMP signalling inhibition by the cystine knot protein Noggin","volume":"420","author":"Groppe","year":"2002","journal-title":"Nature"},{"key":"ref_101","first-page":"214","article-title":"Ectopic Noggin in a Population of Nfatc1 Lineage Endocardial Progenitors Induces Embryonic Lethality","volume":"1","author":"Snider","year":"2014","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ydbio.2005.01.005","article-title":"BMP4 and noggin control embryonic blood vessel formation by antagonistic regulation of VEGFR-2 (Quek1) expression","volume":"280","author":"Nimmagadda","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature13146","article-title":"Endothelial Notch activity promotes angiogenesis and osteogenesis in bone","volume":"507","author":"Ramasamy","year":"2014","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S1097-2765(00)80067-2","article-title":"The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities","volume":"1","author":"Hsu","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/CIRCULATIONAHA.111.038125","article-title":"Gremlin plays a key role in the pathogenesis of pulmonary hypertension","volume":"125","author":"Cahill","year":"2012","journal-title":"Circulation"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, M., Xie, W., Wan, J., Tao, X., Liu, M., Zhen, Y., Lin, F., Wu, B., and Zhai, Z. (2020). Gremlin-1 is a key regulator of endothelial-to-mesenchymal transition in human pulmonary artery endothelial cells. Exp. Cell Res., 390.","DOI":"10.1016\/j.yexcr.2020.111941"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1182\/blood-2010-06-291930","article-title":"Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2","volume":"116","author":"Mitola","year":"2010","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"35353","DOI":"10.18632\/oncotarget.9286","article-title":"Monomeric gremlin is a novel vascular endothelial growth factor receptor-2 antagonist","volume":"7","author":"Grillo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1182\/blood-2006-06-032276","article-title":"Bone morphogenic protein antagonist Drm\/gremlin is a novel proangiogenic factor","volume":"109","author":"Stabile","year":"2007","journal-title":"Blood"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1083\/jcb.200808064","article-title":"A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling","volume":"184","author":"Kelley","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1161\/ATVBAHA.111.230235","article-title":"Bone morphogenetic protein endothelial cell precursor-derived regulator regulates retinal angiogenesis in vivo in a mouse model of oxygen-induced retinopathy","volume":"31","author":"Ren","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_112","first-page":"3082","article-title":"Antagonism and synergy between extracellular bmp modulators tsg and bmper balance blood vessel formation","volume":"126","author":"Heinke","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.matbio.2018.08.006","article-title":"Internal cleavage and synergy with twisted gastrulation enhance BMP inhibition by BMPER","volume":"77","author":"Lim","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1111\/febs.14414","article-title":"Extracellular bone morphogenetic protein modulator BMPER and twisted gastrulation homolog 1 preserve arterial-venous specification in zebrafish blood vessel development and regulate Notch signaling in endothelial cells","volume":"285","author":"Esser","year":"2018","journal-title":"FEBS J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5040","DOI":"10.1182\/blood-2011-03-339762","article-title":"BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium","volume":"118","author":"Helbing","year":"2011","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Guillot, N., Kollins, D., Badimon, J.J., Schlondorff, D., and Hutter, R. (2013). Accelerated reendothelialization, increased neovascularization and erythrocyte extravasation after arterial injury in BAMBI-\/- Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058550"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6861","DOI":"10.1167\/iovs.14-14091","article-title":"R-spondin1 regulates cell proliferation of corneal endothelial cells via the Wnt3a\/\u03b2-catenin pathway","volume":"55","author":"Okumura","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"10719","DOI":"10.1038\/s41598-018-29100-7","article-title":"Intestinal Lymphatic Endothelial Cells Produce R-Spondin3","volume":"8","author":"Ogasawara","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5570","DOI":"10.1038\/s41467-020-19373-w","article-title":"R-spondins are BMP receptor antagonists in Xenopus early embryonic development","volume":"11","author":"Lee","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Tanaka, K., Joshi, D., Timalsina, S., and Schwartz, M.A. (2021). Early events in endothelial flow sensing. Cytoskeleton.","DOI":"10.1002\/cm.21652"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1172\/JCI83083","article-title":"Endothelial fluid shear stress sensing in vascular health and disease","volume":"126","author":"Baeyens","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrm3176","article-title":"Molecular control of endothelial cell behaviour during blood vessel morphogenesis","volume":"12","author":"Herbert","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"31128","DOI":"10.1074\/jbc.M300703200","article-title":"Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response","volume":"278","author":"Sorescu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Ruter, D.L., Liu, Z., Ngo, K.M., Shaka, X., Marvin, A., Buglak, D.B., Kidder, E.J., and Bautch, V.L. (2021). SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis. Angiogenesis.","DOI":"10.1007\/s10456-021-09777-7"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1007\/s00018-007-7166-z","article-title":"Extracellular microfibrils in development and disease","volume":"64","author":"Ramirez","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.tcb.2004.10.003","article-title":"TGF-\u03b2 activation by traction?","volume":"14","author":"Koli","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1083\/jcb.200105046","article-title":"Regulation of limb patterning by extracellular microfibrils","volume":"154","author":"Gayraud","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Kniazeva, E., and Putnam, A.J. (2009). Endothelial cell traction and ECM density influence both capillary morphogenesis and maintenance in 3-D. Am. J. Physiol. Cell Physiol., 297.","DOI":"10.1152\/ajpcell.00018.2009"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.atherosclerosis.2010.04.023","article-title":"Bone morphogenetic protein-2 may represent the molecular link between oxidative stress and vascular stiffness in chronic kidney disease","volume":"211","author":"Dalfino","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s13239-018-0363-0","article-title":"The Roles of Matrix Stiffness and \u00df-Catenin Signaling in Endothelial-to-Mesenchymal Transition of Aortic Valve Endothelial Cells","volume":"9","author":"Zhong","year":"2018","journal-title":"Cardiovasc. Eng. Technol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1083\/jcb.200704010","article-title":"Sequential roles for myosin-X in BMP6-dependent filopodial extension, migration, and activation of BMP receptors","volume":"179","author":"Pi","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1126\/science.1168441","article-title":"Mechanically activated integrin switch controls \u03b15\u03b2 1 function","volume":"323","author":"Friedland","year":"2009","journal-title":"Science"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/jth.12159","article-title":"BMP receptor-integrin interaction mediates responses of vascular endothelial Smad1\/5 and proliferation to disturbed flow","volume":"11","author":"Zhou","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"7770","DOI":"10.1073\/pnas.1205476109","article-title":"Force-specific activation of Smad1\/5 regulates vascular endothelial cell cycle progression in response to disturbed flow","volume":"109","author":"Zhou","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Peacock, H.M., Tabibian, A., Criem, N., Caolo, V., Hamard, L., Deryckere, A., Haefliger, J.-A., Kwak, B.R., Zwijsen, A., and Jones, E.A.V. (2020). Impaired SMAD1\/5 Mechanotransduction and Cx37 (Connexin37) expression enable pathological vessel enlargement and shunting. Arterioscler. Thromb. Vasc. Biol.","DOI":"10.1161\/ATVBAHA.119.313122"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1161\/ATVBAHA.115.306719","article-title":"Interaction between ALK1 signaling and Connexin40 in the development of arteriovenous malformations","volume":"36","author":"Gkatzis","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Baeyens, N., Larriv\u00e9e, B., Ola, R., Hayward-Piatkowskyi, B., Dubrac, A., Huang, B., Ross, T.D., Coon, B.G., Min, E., and Tsarfati, M. (2016). Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia. J. Cell Biol., 214.","DOI":"10.1083\/jcb.201603106"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Santos-Oliveira, P., Correia, A., Rodrigues, T., Ribeiro-Rodrigues, T.M., Matafome, P., Rodr\u00edguez-Manzaneque, J.C., Sei\u00e7a, R., Gir\u00e3o, H., and Travasso, R.D.M. (2015). The force at the tip\u2014Modelling tension and proliferation in sprouting angiogenesis. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004436"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1172\/JCI80454","article-title":"FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature","volume":"125","author":"Sabine","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1172\/JCI79386","article-title":"Lymph flow regulates collecting lymphatic vessel maturation in vivo","volume":"125","author":"Sweet","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Frye, M., Taddei, A., Dierkes, C., Martinez-Corral, I., Fielden, M., Orts\u00e4ter, H., Kazenwadel, J., Calado, D.P., Ostergaard, P., and Salminen, M. (2018). Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-03959-6"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e21498","DOI":"10.1096\/fj.202002426RR","article-title":"Matrix stiffness primes lymphatic tube formation directed by vascular endothelial growth factor-C","volume":"35","author":"Alderfer","year":"2021","journal-title":"FASEB J."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.devcel.2009.06.017","article-title":"Integrin-\u03b19 is required for fibronectin matrix assembly during lymphatic valve morphogenesis","volume":"17","author":"Bazigou","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/emboj.2011.456","article-title":"Mechanoinduction of lymph vessel expansion","volume":"31","author":"Goedecke","year":"2012","journal-title":"EMBO J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1007\/s00018-013-1358-5","article-title":"Mechanical forces in lymphatic vascular development and disease","volume":"70","author":"Lammert","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1161\/CIRCRESAHA.109.206326","article-title":"Endothelial cell adhesion to the extracellular matrix induces c-Src-dependent VEGFR-3 phosphorylation without the activation of the receptor intrinsic kinase activity","volume":"106","author":"Galvagni","year":"2010","journal-title":"Circ. Res."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Hadizadeh, M., Mohaddes Ardebili, S.M., Salehi, M., Young, M., Mokarian, F., McClellan, J., Xu, Q., Kazemi, M., Moazam, E., and Mahaki, B. (2018). GJA4\/connexin 37 mutations correlate with secondary lymphedema following surgery in breast cancer patients. Biomedicines, 6.","DOI":"10.3390\/biomedicines6010023"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ydbio.2011.04.004","article-title":"Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax","volume":"354","author":"Kanady","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-3-7091-1646-3_6","article-title":"V Interplay of mechanotransduction, FOXC2, connexins, and calcineurin signaling in lymphatic valve formation","volume":"214","author":"Sabine","year":"2014","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ydbio.2016.11.017","article-title":"Defective lymphatic valve development and chylothorax in mice with a lymphatic-specific deletion of Connexin43","volume":"421","author":"Munger","year":"2017","journal-title":"Dev. Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ydbio.2016.02.033","article-title":"Segregated Foxc2, NFATc1 and Connexin expression at normal developing venous valves, and Connexin-specific differences in the valve phenotypes of Cx37, Cx43, and Cx47 knockout mice","volume":"412","author":"Munger","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.febslet.2014.01.011","article-title":"Connexins in lymphatic vessel physiology and disease","volume":"588","author":"Meens","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ydbio.2015.06.004","article-title":"Combining Foxc2 and Connexin37 deletions in mice leads to severe defects in lymphatic vascular growth and remodeling","volume":"405","author":"Kanady","year":"2015","journal-title":"Dev. Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.devcel.2011.12.020","article-title":"Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation","volume":"22","author":"Sabine","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1084\/jem.20062596","article-title":"Functionally specialized junctions between endothelial cells of lymphatic vessels","volume":"204","author":"Baluk","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1016\/j.ajpath.2012.02.019","article-title":"Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation","volume":"180","author":"Yao","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.devcel.2009.01.004","article-title":"The control of vascular integrity by endothelial cell junctions: Molecular basis and pathological implications","volume":"16","author":"Dejana","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"H\u00e4gerling, R., Hoppe, E., Dierkes, C., Stehling, M., Makinen, T., Butz, S., Vestweber, D., and Kiefer, F. (2018). Distinct roles of VE -cadherin for development and maintenance of specific lymph vessel beds. EMBO J., 37.","DOI":"10.15252\/embj.201798271"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/j.celrep.2019.07.072","article-title":"VE-cadherin is required for lymphatic valve formation and maintenance","volume":"28","author":"Yang","year":"2019","journal-title":"Cell Rep."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Zwijsen, A., van Rooijen, M., Goumans, M., Dewulf, N., Bosman, E., ten Dijke, P., Mummery, C., and Huylebroeck, D. (2000). Expression of the inhibitory Smad7 in early mouse development and upregulation during embryonic vasculogenesis. Dev. Dyn., 218.","DOI":"10.1002\/1097-0177(200008)218:4<663::AID-DVDY1020>3.0.CO;2-7"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Murayama, K., Kato-Murayama, M., Itoh, Y., Miyazono, K., Miyazawa, K., and Shirouzu, M. (2020). Structural basis for inhibitory effects of Smad7 on TGF-\u03b2 family signaling. J. Struct. Biol., 212.","DOI":"10.1016\/j.jsb.2020.107661"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"20603","DOI":"10.1074\/jbc.M702100200","article-title":"Selective inhibitory effects of Smad6 on bone morphogenetic protein type I receptors","volume":"282","author":"Goto","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ydbio.2018.07.027","article-title":"Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted endothelial cell junctions","volume":"442","author":"Wylie","year":"2018","journal-title":"Dev. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1091\/mbc.e02-07-0441","article-title":"Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads","volume":"14","author":"Murakami","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"12477","DOI":"10.1074\/jbc.C100008200","article-title":"Smurf1 interacts with transforming growth Factor-\u03b2 Type I receptor through smad7 and induces receptor degradation","volume":"276","author":"Ebisawa","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1080\/10409238.2020.1828260","article-title":"Current perspectives on inhibitory SMAD7 in health and disease","volume":"55","author":"Spit","year":"2020","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Mouillesseaux, K.P., Wiley, D.S., Saunders, L.M., Wylie, L.A., Kushner, E.J., Chong, D.C., Citrin, K.M., Barber, A.T., Park, Y., and Kim, J.D. (2016). Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6. Nat. Commun., 7.","DOI":"10.1038\/ncomms13247"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1007\/s11605-016-3294-9","article-title":"Expression of VEGF-D, SMAD4, and SMAD7 and their relationship with lymphangiogenesis and prognosis in colon cancer","volume":"20","author":"Su","year":"2016","journal-title":"J. Gastrointest. Surg."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cytogfr.2011.11.006","article-title":"Few Smad proteins and many Smad-interacting proteins yield multiple functions and action modes in TGF\u03b2\/BMP signaling in vivo","volume":"22","author":"Conidi","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"G803","DOI":"10.1152\/ajpgi.00215.2019","article-title":"Unraveling the transcriptional determinants of liver sinusoidal endothelial cell specialization","volume":"318","author":"Benkheil","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"De Haan, W., Dheedene, W., Apelt, K., D\u00e9combas-Deschamps, S., Vinckier, S., Verhulst, S., Conidi, A., Deffieux, T., Staring, M.W., and Vandervoort, P. (2021). Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvab148"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1128\/MCB.00231-12","article-title":"Transforming growth factor inhibits bone morphogenetic protein-induced transcription through novel phosphorylated Smad1\/5-Smad3 complexes","volume":"32","author":"Gronroos","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00441-017-2757-y","article-title":"TGF-\u03b2 signaling inhibits canonical BMP signaling pathway during palate development","volume":"371","author":"Yuan","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1242\/dev.095026","article-title":"suke TGF\u03b2 signaling is required for sprouting lymphangiogenesis during lymphatic network development in the skin","volume":"140","author":"James","year":"2013","journal-title":"Development"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1002\/jcp.24063","article-title":"TGF\u03b21 inhibits lymphatic endothelial cell differentiation from mouse embryonic stem cells","volume":"227","author":"Vittet","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.1182\/blood-2007-10-120337","article-title":"Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis","volume":"111","author":"Oka","year":"2008","journal-title":"Blood"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"12960","DOI":"10.1073\/pnas.1301415110","article-title":"Structural and mechanistic insights into VEGF receptor 3 ligand binding and activation","volume":"110","author":"Tvorogov","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev-cellbio-092910-154002","article-title":"Developmental and pathological angiogenesis","volume":"27","author":"Chung","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1242\/dev.063933","article-title":"Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo","volume":"138","author":"Krueger","year":"2011","journal-title":"Development"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Pulkkinen, H.H., Kiema, M., Lappalainen, J.P., Toropainen, A., Beter, M., Tirronen, A., Holappa, L., Niskanen, H., Kaikkonen, M.U., and Yl\u00e4-Herttuala, S. (2020). BMP6\/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF. Angiogenesis, 24.","DOI":"10.1007\/s10456-020-09748-4"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1242\/dev.097360","article-title":"Bmp signaling represses vegfa to promote outflow tract cushion development","volume":"140","author":"Bai","year":"2013","journal-title":"Development"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1182\/blood-2009-01-199166","article-title":"Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells","volume":"114","author":"Shao","year":"2009","journal-title":"Blood"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s10456-019-09676-y","article-title":"VEGFR2 activation mediates the pro-angiogenic activity of BMP4","volume":"22","author":"Rezzola","year":"2019","journal-title":"Angiogenesis"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/ncb1486","article-title":"VEGF Controls endothelial-cell permeability promoting \u03b2-arrestin-dependent Endocytosis VE-cadherin","volume":"8","author":"Gavard","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/micc.12124","article-title":"Neuropilin regulation of angiogenesis, arteriogenesis, and vascular permeability","volume":"21","author":"Plein","year":"2014","journal-title":"Microcirculation"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1161\/01.RES.0000171756.13554.49","article-title":"Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability","volume":"96","author":"Becker","year":"2005","journal-title":"Circ. Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1161\/ATVBAHA.118.310733","article-title":"BMP9 (bone morphogenetic protein-9)\/ALK1 (activin-like kinase receptor type I) signaling prevents hyperglycemia-induced vascular permeability","volume":"38","author":"Akla","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"4843","DOI":"10.1128\/MCB.02214-07","article-title":"Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos","volume":"28","author":"Haiko","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/ni1013","article-title":"Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins","volume":"5","author":"Karkkainen","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1038\/onc.2011.602","article-title":"Interaction of tumor cells and lymphatic vessels in cancer progression","volume":"31","author":"Alitalo","year":"2012","journal-title":"Oncogene"},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Jeltsch, M., Lepp\u00e4nen, V.M., Saharinen, P., and Alitalo, K. (2013). Receptor tyrosine Kinase-Mediated angiogenesis. Cold Spring Harb. Perspect. Med., 3.","DOI":"10.1101\/cshperspect.a009183"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1161\/CIRCRESAHA.113.300350","article-title":"Mutation in vascular endothelial growth factor-c, a ligand for vascular endothelial growth factor receptor-3, is associated with autosomal dominant milroy-like primary lymphedema","volume":"112","author":"Gordon","year":"2013","journal-title":"Circ. Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"12677","DOI":"10.1073\/pnas.221449198","article-title":"A model for gene therapy of human hereditary lymphedema","volume":"98","author":"Karkkainen","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/dvdy.24227","article-title":"VEGFR signaling during lymphatic vascular development: From progenitor cells to functional vessels","volume":"244","author":"Secker","year":"2015","journal-title":"Dev. Dyn."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.devcel.2017.04.001","article-title":"The canonical notch signaling pathway: Structural and biochemical insights into shape, sugar, and force","volume":"41","author":"Kovall","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Morikawa, M., Koinuma, D., Tsutsumi, S., Vasilaki, E., Kanki, Y., Heldin, C.H., Aburatani, H., and Miyazono, K. (2011). ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif. Nucleic Acids Res.","DOI":"10.1093\/nar\/gkr572"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/sj.emboj.7600065","article-title":"Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells","volume":"23","author":"Itoh","year":"2004","journal-title":"EMBO J."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/cvr\/cvv148","article-title":"Context-specific interactions between Notch and ALK1 cannot explain ALK1-associated arteriovenous malformations","volume":"107","author":"Rochon","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"W\u00f6ltje, K., Jabs, M., and Fischer, A. (2015). Serum Induces transcription of Hey1 and Hey2 genes by Alk1 but not notch signaling in endothelial cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120547"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"6162","DOI":"10.1182\/blood-2012-01-407593","article-title":"BMP9 and BMP10 are critical for postnatal retinal vascular remodeling","volume":"119","author":"Ricard","year":"2012","journal-title":"Blood"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.devcel.2012.02.005","article-title":"ALK1 signaling inhibits angiogenesis by cooperating with the notch pathway","volume":"22","author":"Prahst","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1172\/JCI42666","article-title":"Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation","volume":"120","author":"Prados","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1007\/s00018-012-1197-9","article-title":"Co-ordinating Notch, BMP, and TGF-\u03b2 signaling during heart valve development","volume":"70","author":"Garside","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.tig.2012.11.008","article-title":"Robustness in angiogenesis: Notch and BMP shaping waves","volume":"29","author":"Beets","year":"2013","journal-title":"Trends Genet."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.devcel.2007.05.014","article-title":"Id sustains Hes1 expression to inhibit precocious neurogenesis by releasing negative autoregulation of Hes1","volume":"13","author":"Bai","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1182\/blood-2010-11-317800","article-title":"Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor","volume":"118","author":"Zheng","year":"2011","journal-title":"Blood"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1242\/dev.101188","article-title":"Notch signaling functions in lymphatic valve formation","volume":"141","author":"Murtomaki","year":"2014","journal-title":"Development"},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Michelini, S., Ricci, M., Serrani, R., Barati, S., Kenanoglu, S., Veselenyiova, D., Kurti, D., Baglivo, M., Basha, S.H., and Priya, S. (2021). NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants. Mol. Genet. Genomic Med., 9.","DOI":"10.1002\/mgg3.1529"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1172\/JCI82045","article-title":"DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport","volume":"125","author":"Cisarovsky","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.gde.2009.09.004","article-title":"Vascular morphogenesis: A Wnt for every vessel?","volume":"19","author":"Franco","year":"2009","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1534\/genetics.112.144592","article-title":"Structure-function dissection of the Frizzled receptor in Drosophila melanogaster suggests different mechanisms of action in planar polarity and canonical Wnt signaling","volume":"192","author":"Strutt","year":"2012","journal-title":"Genetics"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.molcel.2016.08.026","article-title":"Wnt signalosome assembly by DEP domain swapping of dishevelled","volume":"64","author":"Gammons","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s00018-017-2654-2","article-title":"The function of endocytosis in Wnt signaling","volume":"75","author":"Brunt","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/CIRCRESAHA.109.196063","article-title":"Tbx20 interacts with smads to confine tbx2 expression to the atrioventricular canal","volume":"105","author":"Singh","year":"2009","journal-title":"Circ. Res."},{"key":"ref_215","first-page":"497","article-title":"\u03b2-catenin-dependent transcription is central to bmp-mediated formation of venous vessels","volume":"142","author":"Kashiwada","year":"2015","journal-title":"Development"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1101\/gad.282400.116","article-title":"Mechanotransduction activates canonical Wnt\/\u03b2-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves","volume":"30","author":"Cha","year":"2016","journal-title":"Genes Dev."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"403","DOI":"10.5483\/BMBRep.2016.49.8.112","article-title":"Mechanosensitive \u03b2-catenin signaling regulates lymphatic vascular development","volume":"49","author":"Cha","year":"2016","journal-title":"BMB Rep."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.celrep.2018.09.049","article-title":"Complementary wnt sources regulate lymphatic vascular development via PROX1-Dependent Wnt\/\u03b2-catenin signaling","volume":"25","author":"Cha","year":"2018","journal-title":"Cell Rep."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature14425","article-title":"Lymphatic vessels arise from specialized angioblasts within a venous niche","volume":"522","author":"Nicenboim","year":"2015","journal-title":"Nature"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1182\/blood.2019004560","article-title":"Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia","volume":"136","author":"Shovlin","year":"2020","journal-title":"Blood"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng0696-189","article-title":"Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type","volume":"13","author":"Johnson","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ng1294-345","article-title":"Endoglin, a TGF-\u03b2 binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1","volume":"8","author":"McAllister","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S0140-6736(04)15732-2","article-title":"A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4)","volume":"363","author":"Gallione","year":"2004","journal-title":"Lancet"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.ajhg.2013.07.004","article-title":"BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia","volume":"93","author":"McDonald","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Hernandez, F., Huether, R., Carter, L., Johnston, T., Thompson, J., Gossage, J.R., Chao, E., and Elliott, A.M. (2015). Mutations in RASA1 and GDF2 identified in patients with clinical features of hereditary hemorrhagic telangiectasia. Hum. Genome Var., 2.","DOI":"10.1038\/hgv.2015.40"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"470","DOI":"10.3171\/jns.2007.106.3.470","article-title":"Growth and regression of arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia. Case report","volume":"106","author":"Du","year":"2007","journal-title":"J. Neurosurg."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/cvr\/cvv264","article-title":"Arteriovenous malformations in hereditary haemorrhagic telangiectasia: Looking beyond ALK1-NOTCH interactions","volume":"109","author":"Peacock","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1159\/000337762","article-title":"Minimal homozygous endothelial deletion of eng with VEGF stimulation is sufficient to cause cerebrovascular dysplasia in the adult mouse","volume":"33","author":"Choi","year":"2012","journal-title":"Cerebrovasc. Dis."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Bernabeu, C., Bayrak-Toydemir, P., McDonald, J., and Letarte, M. (2020). Potential second-hits in hereditary hemorrhagic telangiectasia. J. Clin. Med., 9.","DOI":"10.3390\/jcm9113571"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.drudis.2018.12.001","article-title":"TGF\u03b2 and BMPRII signalling pathways in the pathogenesis of pulmonary arterial hypertension","volume":"24","author":"Tielemans","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrcardio.2017.84","article-title":"Epidemiology and treatment of pulmonary arterial hypertension","volume":"14","author":"Lau","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Morrell, N.W., Aldred, M.A., Chung, W.K., Elliott, C.G., Nichols, W.C., Soubrier, F., Trembath, R.C., and Loyd, J.E. (2019). Genetics and genomics of pulmonary arterial hypertension. Eur. Respir. J., 53.","DOI":"10.1183\/13993003.01899-2018"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1086\/303059","article-title":"Familial primary pulmonary hypertension (Gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene","volume":"67","author":"Deng","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/79226","article-title":"Heterozygous germline mutations in BMPR2, encoding a TGF-\u03b2 receptor, cause familial primary pulmonary hypertension","volume":"26","author":"Lane","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nm.3877","article-title":"Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension","volume":"21","author":"Long","year":"2015","journal-title":"Nat. Med."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1113\/EP086041","article-title":"Bone morphogenetic protein signalling in pulmonary hypertension: Advances and therapeutic implications","volume":"102","author":"Yang","year":"2017","journal-title":"Exp. Physiol."},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Hiepen, C., Jatzlau, J., Hildebrandt, S., Kampfrath, B., Goktas, M., Murgai, A., Cuellar Camacho, J.L., Haag, R., Ruppert, C., and Sengle, G. (2019). BMPR2 acts as a gatekeeper to protect endothelial cells from increased TGF\u03b2 responses and altered cell mechanics. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000557"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S2213-2600(15)00544-5","article-title":"BMPR2 mutations and survival in pulmonary arterial hypertension: An individual participant data meta-analysis","volume":"4","author":"Evans","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1161\/STROKEAHA.118.022314","article-title":"Familial Cerebral Cavernous Malformations","volume":"50","author":"Zafar","year":"2019","journal-title":"Stroke"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/nature12207","article-title":"EndMT contributes to the onset and progression of cerebral cavernous malformations","volume":"498","author":"Maddaluno","year":"2013","journal-title":"Nature"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.jacc.2009.12.068","article-title":"Bicuspid Aortic Valve Disease","volume":"55","author":"Siu","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Balistreri, C.R., Crapanzano, F., Schirone, L., Allegra, A., Pisano, C., Ruvolo, G., Forte, M., Greco, E., Cavarretta, E., and Marullo, A.G.M. (2018). Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-32170-2"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/s41431-019-0363-z","article-title":"Confirmation of the role of pathogenic SMAD6 variants in bicuspid aortic valve-related aortopathy","volume":"27","author":"Luyckx","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1161\/ATVBAHA.111.242594","article-title":"Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis","volume":"32","author":"Derwall","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1161\/ATVBAHA.111.240101","article-title":"Pharmacological suppression of hepcidin increases macrophage cholesterol efflux and reduces foam cell formation and atherosclerosis","volume":"32","author":"Saeed","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1083\/jcb.201502003","article-title":"Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response","volume":"210","author":"Vandersmissen","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.yjmcc.2010.01.010","article-title":"Bone morphogenetic protein 4 mediates myocardial ischemic injury through JNK-dependent signaling pathway","volume":"48","author":"Pachori","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1161\/ATVBAHA.110.206185","article-title":"Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo","volume":"30","author":"Nakagawa","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1172\/JCI116391","article-title":"Bone morphogenetic protein expression in human atherosclerotic lesions","volume":"91","author":"Watson","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.redox.2017.01.007","article-title":"Angiogenesis in the atherosclerotic plaque","volume":"12","author":"Pucelle","year":"2017","journal-title":"Redox Biol."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1016\/j.atherosclerosis.2017.06.129","article-title":"Inhibition of VEGF receptor signaling attenuates intraplaque angiogenesis and plaque destabilization in a mouse model of advanced atherosclerosis","volume":"263","author":"Martinet","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/ng1783","article-title":"A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva","volume":"38","author":"Shore","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.humpath.2017.03.005","article-title":"Vascular patterning in human heterotopic ossification","volume":"63","author":"Cocks","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.cell.2020.06.039","article-title":"The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease","volume":"182","author":"Oliver","year":"2020","journal-title":"Cell"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1089\/lrb.2017.0083","article-title":"Breast cancer-related lymphedema and genetic predisposition: A systematic review of the literature","volume":"17","author":"Visser","year":"2019","journal-title":"Lymphat. Res. Biol."},{"key":"ref_256","doi-asserted-by":"crossref","unstructured":"Kim, T., Tafoya, E., Chelliah, M.P., Lekwuttikarn, R., Li, J., Sarin, K.Y., and Teng, J. (2019). Alterations of the MEK\/ERK, BMP, and Wnt\/\u03b2-catenin pathways detected in the blood of individuals with lymphatic malformations. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213872"},{"key":"ref_257","doi-asserted-by":"crossref","unstructured":"Miaskowski, C., Dodd, M., Paul, S.M., West, C., Hamolsky, D., Abrams, G., Cooper, B.A., Elboim, C., Neuhaus, J., and Schmidt, B.L. (2013). Lymphatic and angiogenic candidate genes predict the development of secondary lymphedema following breast cancer surgery. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060164"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.lfs.2019.04.038","article-title":"miR-27a promotes endothelial-mesenchymal transition in hypoxia-induced pulmonary arterial hypertension by suppressing BMP signaling","volume":"227","author":"Liu","year":"2019","journal-title":"Life Sci."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.bbrc.2009.12.170","article-title":"Endothelial cells are activated during hypoxia via endoglin\/ALK-1\/SMAD1\/5 signaling in vivo and in vitro","volume":"392","author":"Tian","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:14:10Z","timestamp":1760163250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,14]]},"references-count":259,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22126364"],"URL":"https:\/\/doi.org\/10.3390\/ijms22126364","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,14]]}}}