{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:53:30Z","timestamp":1792155210287,"version":"4.4.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The lymphatic system is crucial for the maintenance of interstitial fluid and protein homeostasis. It has important roles in collecting excess plasma and interstitial fluid leaked from blood vessels, lipid absorption and transportation in the digestive system, and immune surveillance and response. The development of lymphatic vessels begins during fetal life as lymphatic endothelial progenitor cells first differentiate into lymphatic endothelial cells (LECs) by expressing the master lymphatic vascular regulator, prospero-related homeobox 1 (PROX1). The lymphatic vasculature forms a hierarchical network that consists of blind-ended and unidirectional vessels. Although much progress has been made in the elucidation of the cellular and molecular mechanisms underlying the formation of the lymphatic vascular system, the causes of lymphatic vessel abnormalities and disease are poorly understood and complicated; specifically, the mechanistic basis for transcriptional dysregulation in lymphatic vessel development remains largely unclear. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms of lymphatic vascular development, including LEC differentiation, lymphangiogenesis, and valve formation, and the significance of mechanical forces in lymphatic vessels, with a focus on transcriptional regulation. We also summarize the current knowledge on epigenetic mechanisms of lymphatic gene expression.<\/jats:p>","DOI":"10.3389\/fphys.2022.1066460","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T03:03:34Z","timestamp":1668049414000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation"],"prefix":"10.3389","volume":"13","author":[{"given":"Naoto","family":"Ujiie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Kume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1177\/1535370217697385","article-title":"Lymphangiogenesis: Fuel, smoke, or extinguisher of inflammation's fire?","volume":"242","author":"Abouelkheir","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/nature04480","article-title":"Lymphangiogenesis in development and human disease","volume":"438","author":"Alitalo","year":"2005","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1038\/nm.2545","article-title":"The lymphatic vasculature in disease","volume":"17","author":"Alitalo","year":"2011","journal-title":"Nat. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"110982","DOI":"10.1016\/j.celrep.2022.110982","article-title":"Mafba and mafbb differentially regulate lymphatic endothelial cell migration in topographically distinct manners","volume":"39","author":"Arnold","year":"2022","journal-title":"Cell Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1161\/CIRCRESAHA.115.306436","article-title":"Meet me in the middle: Dual origins of dermal lymphatic vasculature in mammals","volume":"116","author":"Bernier-Latmani","year":"2015","journal-title":"Circ. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1161\/CIRCRESAHA.118.313707","article-title":"YAP and TAZ negatively regulate Prox1 during developmental and pathologic lymphangiogenesis","volume":"124","author":"Cho","year":"2019","journal-title":"Circ. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"125068","DOI":"10.1172\/jci.insight.125068","article-title":"Piezo1 incorporates mechanical force signals into the genetic program that governs lymphatic valve development and maintenance","volume":"4","author":"Choi","year":"2019","journal-title":"JCI Insight"},{"key":"B8","doi-asserted-by":"publisher","first-page":"a006445","DOI":"10.1101\/cshperspect.a006445","article-title":"The new era of the lymphatic system: No longer secondary to the blood vascular system","volume":"2","author":"Choi","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2614","DOI":"10.1182\/blood-2013-12-297317","article-title":"Pressing the right buttons: Signaling in lymphangiogenesis","volume":"123","author":"Coso","year":"2014","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1172\/JCI84652","article-title":"CHD4-regulated plasmin activation impacts lymphovenous hemostasis and hepatic vascular integrity","volume":"126","author":"Crosswhite","year":"2016","journal-title":"J. Clin."},{"key":"B11","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/s41586-022-04766-2","article-title":"Generation of specialized blood vessels via lymphatic transdifferentiation","volume":"606","author":"Das","year":"2022","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1242\/dev.087379","article-title":"BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development","volume":"140","author":"Davis","year":"2013","journal-title":"Development"},{"key":"B13","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1084\/jem.20021346","article-title":"The formation of lymphatic vessels and its importance in the setting of malignancy","volume":"196","author":"Detmar","year":"2002","journal-title":"J. Exp. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.celrep.2015.10.002","article-title":"DeepCAGE transcriptomics reveal an important role of the transcription factor MAFB in the lymphatic endothelium","volume":"13","author":"Dieterich","year":"2015","journal-title":"Cell Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s10456-020-09721-1","article-title":"Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis","volume":"23","author":"Dieterich","year":"2020","journal-title":"Angiogenesis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.devcel.2021.01.018","article-title":"Beyond PROX1: Transcriptional, epigenetic, and noncoding RNA regulation of lymphatic identity and function","volume":"56","author":"Ducoli","year":"2021","journal-title":"Dev. Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1146\/annurev-cellbio-111315-124944","article-title":"Lymphangiogenesis: Origin, specification, and cell fate determination","volume":"32","author":"Escobedo","year":"2016","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"B18","doi-asserted-by":"publisher","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":"B19","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1172\/JCI80465","article-title":"Foxc1 and Foxc2 deletion causes abnormal lymphangiogenesis and correlates with ERK hyperactivation","volume":"126","author":"Fatima","year":"2016","journal-title":"J. Clin. Invest."},{"key":"B20","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nature07391","article-title":"Sox18 induces development of the lymphatic vasculature in mice","volume":"456","author":"Francois","year":"2008","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.ydbio.2011.12.032","article-title":"Segmental territories along the cardinal veins generate lymph sacs via a ballooning mechanism during embryonic lymphangiogenesis in mice","volume":"364","author":"Francois","year":"2012","journal-title":"Dev. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2704","DOI":"10.1038\/s41467-018-05039-1","article-title":"HHEX is a transcriptional regulator of the VEGFC\/FLT4\/PROX1 signaling axis during vascular development","volume":"9","author":"Gauvrit","year":"2018","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/emboj.2012.340","article-title":"A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy","volume":"32","author":"Hagerling","year":"2013","journal-title":"EMBO J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e107192","DOI":"10.15252\/embj.2020107192","article-title":"Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels","volume":"40","author":"Hernandez Vasquez","year":"2021","journal-title":"EMBO J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e51639","DOI":"10.1371\/journal.pone.0051639","article-title":"Ras\/MAPK signaling modulates VEGFR-3 expression through Ets-mediated p300 recruitment and histone acetylation on the Vegfr3 gene in lymphatic endothelial cells","volume":"7","author":"Ichise","year":"2012","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1004031","DOI":"10.1371\/journal.pgen.1004031","article-title":"The NuRD chromatin-remodeling enzyme CHD4 promotes embryonic vascular integrity by transcriptionally regulating extracellular matrix proteolysis","volume":"9","author":"Ingram","year":"2013","journal-title":"PLoS Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"4193","DOI":"10.1172\/JCI92852","article-title":"Hdac3 regulates lymphovenous and lymphatic valve formation","volume":"127","author":"Janardhan","year":"2017","journal-title":"J. Clin. Invest."},{"key":"B28","doi-asserted-by":"publisher","first-page":"4759","DOI":"10.1182\/blood-2010-12-327668","article-title":"Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation","volume":"117","author":"Jo","year":"2011","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","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":"B30","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.1172\/JCI78888","article-title":"GATA2 is required for lymphatic vessel valve development and maintenance","volume":"125","author":"Kazenwadel","year":"2015","journal-title":"J. Clin."},{"key":"B31","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/dvdy.24313","article-title":"Morphogenesis of the lymphatic vasculature: A focus on new progenitors and cellular mechanisms important for constructing lymphatic vessels","volume":"245","author":"Kazenwadel","year":"2016","journal-title":"Dev. Dyn."},{"key":"B32","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/nature14483","article-title":"Cardiac lymphatics are heterogeneous in origin and respond to injury","volume":"522","author":"Klotz","year":"2015","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1172\/JCI83189","article-title":"Lymphatic vessel development: Fluid flow and valve-forming cells","volume":"125","author":"Kume","year":"2015","journal-title":"J. Clin."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e2101931118","DOI":"10.1073\/pnas.2101931118","article-title":"Investigating lymphangiogenesis in vitro and in vivo using engineered human lymphatic vessel networks","volume":"118","author":"Landau","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1182\/blood-2008-03-145789","article-title":"Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate","volume":"113","author":"Lee","year":"2009","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","first-page":"eabe7359","DOI":"10.1126\/sciadv.abe7359","article-title":"Mitochondrial respiration controls the Prox1-Vegfr3 feedback loop during lymphatic endothelial cell fate specification and maintenance","volume":"7","author":"Ma","year":"2021","journal-title":"Sci. Adv."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1161\/CIRCRESAHA.116.306170","article-title":"Nonvenous origin of dermal lymphatic vasculature","volume":"116","author":"Martinez-Corral","year":"2015","journal-title":"Circ. Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"846936","DOI":"10.3389\/fphys.2022.846936","article-title":"Lymphatic vessel regression and its therapeutic applications: Learning from principles of blood vessel regression","volume":"13","author":"Masood","year":"2022","journal-title":"Front. Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1161\/CIRCULATIONAHA.106.675348","article-title":"Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb","volume":"115","author":"Mellor","year":"2007","journal-title":"Circulation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1101\/gad.2018511","article-title":"DOT1L regulates dystrophin expression and is critical for cardiac function","volume":"25","author":"Nguyen","year":"2011","journal-title":"Genes Dev."},{"key":"B41","doi-asserted-by":"publisher","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":"B42","doi-asserted-by":"publisher","first-page":"dev181545","DOI":"10.1242\/dev.181545","article-title":"FOXO1 regulates developmental lymphangiogenesis by upregulating CXCR4 in the mouse-tail dermis","volume":"147","author":"Niimi","year":"2020","journal-title":"Development"},{"key":"B43","doi-asserted-by":"publisher","first-page":"110048","DOI":"10.1016\/j.celrep.2021.110048","article-title":"FOXO1 represses lymphatic valve formation and maintenance via PRDM1","volume":"37","author":"Niimi","year":"2021","journal-title":"Cell Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"12817","DOI":"10.1073\/pnas.1817070115","article-title":"Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation","volume":"115","author":"Nonomura","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B45","doi-asserted-by":"publisher","first-page":"627647","DOI":"10.3389\/fcell.2020.627647","article-title":"Molecular mechanisms controlling lymphatic endothelial junction integrity","volume":"8","author":"Norden","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e53814","DOI":"10.7554\/eLife.53814","article-title":"Shear stimulation of FOXC1 and FOXC2 differentially regulates cytoskeletal activity during lymphatic valve maturation","volume":"9","author":"Norden","year":"2020","journal-title":"Elife"},{"key":"B47","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1083\/jcb.200901104","article-title":"FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1","volume":"185","author":"Norrmen","year":"2009","journal-title":"J. Cell Biol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.cell.2020.06.039","article-title":"The lymphatic vasculature in the 21(st) century: Novel functional roles in homeostasis and disease","volume":"182","author":"Oliver","year":"2020","journal-title":"Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1038\/nm1094","article-title":"Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis","volume":"10","author":"Petrova","year":"2004","journal-title":"Nat. Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"eaax4063","DOI":"10.1126\/science.aax4063","article-title":"Biological functions of lymphatic vessels","volume":"369","author":"Petrova","year":"2020","journal-title":"Science"},{"key":"B51","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1084\/jem.20171868","article-title":"Organ-specific lymphatic vasculature: From development to pathophysiology","volume":"215","author":"Petrova","year":"2018","journal-title":"J. Exp. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/nrm.2017.36","article-title":"Vascular heterogeneity and specialization in development and disease","volume":"18","author":"Potente","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1146\/annurev-immunol-041015-055354","article-title":"The lymphatic system: Integral roles in immunity","volume":"35","author":"Randolph","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1002\/dvdy.209","article-title":"MAFB modulates the maturation of lymphatic vascular networks in mice","volume":"249","author":"Rondon-Galeano","year":"2020","journal-title":"Dev. Dyn."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.4049\/jimmunol.0804324","article-title":"Secondary lymphoid organs: Responding to genetic and environmental cues in ontogeny and the immune response","volume":"183","author":"Ruddle","year":"2009","journal-title":"J. Immunol."},{"key":"B56","doi-asserted-by":"publisher","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":"B57","doi-asserted-by":"publisher","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."},{"key":"B58","doi-asserted-by":"publisher","first-page":"804675","DOI":"10.1155\/2013\/804675","article-title":"Lymphedema and therapeutic lymphangiogenesis","volume":"2013","author":"Saito","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"B59","doi-asserted-by":"publisher","first-page":"142341","DOI":"10.1172\/JCI142341","article-title":"Foxo1 deletion promotes the growth of new lymphatic valves","volume":"131","author":"Scallan","year":"2021","journal-title":"J. Clin."},{"key":"B60","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1111\/dgd.12757","article-title":"Back and forth: History of and new insights on the vertebrate lymphatic valve","volume":"63","author":"Shin","year":"2021","journal-title":"Dev. Growth Differ."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1101\/gad.216226.113","article-title":"The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors","volume":"28","author":"Srinivasan","year":"2014","journal-title":"Genes Dev."},{"key":"B62","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1101\/gad.1859310","article-title":"The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells","volume":"24","author":"Srinivasan","year":"2010","journal-title":"Genes Dev."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1101\/gad.16974811","article-title":"Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves","volume":"25","author":"Srinivasan","year":"2011","journal-title":"Genes Dev."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1016\/j.celrep.2015.02.026","article-title":"cKit lineage hemogenic endothelium-derived cells contribute to mesenteric lymphatic vessels","volume":"10","author":"Stanczuk","year":"2015","journal-title":"Cell Rep."},{"key":"B65","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.devcel.2019.04.034","article-title":"Paraxial mesoderm is the major source of lymphatic endothelium","volume":"50","author":"Stone","year":"2019","journal-title":"Dev. Cell"},{"key":"B66","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.molmed.2021.07.003","article-title":"Homeostatic maintenance of the lymphatic vasculature","volume":"27","author":"Stritt","year":"2021","journal-title":"Trends Mol. Med."},{"key":"B67","doi-asserted-by":"publisher","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. Invest."},{"key":"B68","doi-asserted-by":"publisher","first-page":"6314","DOI":"10.1038\/s41467-020-20156-6","article-title":"Blood and lymphatic systems are segregated by the FLCN tumor suppressor","volume":"11","author":"Tai-Nagara","year":"2020","journal-title":"Nat. Commun."},{"key":"B69","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.cell.2010.01.045","article-title":"Lymphangiogenesis: Molecular mechanisms and future promise","volume":"140","author":"Tammela","year":"2010","journal-title":"Cell"},{"key":"B70","doi-asserted-by":"publisher","first-page":"54228","DOI":"10.18632\/oncotarget.9797","article-title":"FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function","volume":"7","author":"Tavian","year":"2016","journal-title":"Oncotarget"},{"key":"B71","doi-asserted-by":"publisher","first-page":"6072","DOI":"10.1038\/s41467-021-26346-0","article-title":"Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies","volume":"12","author":"Thomson","year":"2021","journal-title":"Nat. Commun."},{"key":"B72","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/s0002-9394(02)01642-2","article-title":"Lymphedema-distichiasis syndrome and FOXC2 gene mutation","volume":"134","author":"Traboulsi","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"3590","DOI":"10.1242\/dev.147967","article-title":"Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity","volume":"144","author":"Wang","year":"2017","journal-title":"Development"},{"key":"B74","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/s0092-8674(00)81511-1","article-title":"Prox1 function is required for the development of the murine lymphatic system","volume":"98","author":"Wigle","year":"1999","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nature21028","article-title":"The role of fatty acid beta-oxidation in lymphangiogenesis","volume":"542","author":"Wong","year":"2017","journal-title":"Nature"},{"key":"B76","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/j.1365-2443.2008.01279.x","article-title":"COUP-TFII regulates the functions of Prox1 in lymphatic endothelial cells through direct interaction","volume":"14","author":"Yamazaki","year":"2009","journal-title":"Genes"},{"key":"B77","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.1182\/blood-2012-05-428607","article-title":"Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos","volume":"120","author":"Yang","year":"2012","journal-title":"Blood"},{"key":"B78","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1172\/JCI71609","article-title":"Development of the mammalian lymphatic vasculature","volume":"124","author":"Yang","year":"2014","journal-title":"J. Clin. Invest."},{"key":"B79","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/s41419-019-2201-1","article-title":"Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function","volume":"11","author":"Yoo","year":"2020","journal-title":"Cell Death Dis."},{"key":"B80","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1242\/jcs.083998","article-title":"Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1","volume":"124","author":"Yoshimatsu","year":"2011","journal-title":"J. Cell Sci."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.1066460\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T03:03:37Z","timestamp":1668049417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.1066460\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,10]]},"references-count":80,"alternative-id":["10.3389\/fphys.2022.1066460"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.1066460","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,10]]},"article-number":"1066460"}}