{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:59:48Z","timestamp":1779148788337,"version":"3.51.4"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32322028"],"award-info":[{"award-number":["32322028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the National Key R&D Program of China"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In zebrafish, brain lymphatic endothelial cells (BLECs) are essential for meningeal angiogenesis and cerebrovascular regeneration. Although epidermal growth factor-like domain 7 (Egfl7) has been reported to act as a pro-angiogenic factor, its roles in lymphangiogenesis remain unclear. Here, we show that Egfl7 is expressed in both blood and lymphatic endothelial cells. We generate an <jats:italic>egfl7<\/jats:italic><jats:sup><jats:italic>cq180<\/jats:italic><\/jats:sup> mutant with a 13-bp-deletion in exon 3 leading to reduced expression of Egfl7. The <jats:italic>egfl7<\/jats:italic><jats:sup><jats:italic>cq180<\/jats:italic><\/jats:sup> mutant zebrafish exhibit defective formation of BLEC bilateral loop-like structures, although trunk and facial lymphatic development remains unaffected. Moreover, while the <jats:italic>egfl7<\/jats:italic><jats:sup><jats:italic>cq180<\/jats:italic><\/jats:sup> mutant displays normal BLEC lineage specification, the migration and proliferation of these cells are impaired. Additionally, we identify integrin \u03b1v\u03b23 as the receptor for Egfl7. \u03b1v\u03b23 is expressed in the CVP and sprouting BLECs, and blocking this integrin inhibits the formation of BLEC bilateral loop-like structures. Thus, this study identifies a role for Egfl7 in BLEC development that is mediated through the integrin \u03b1v\u03b23.<\/jats:p>","DOI":"10.1038\/s41467-024-50389-8","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T19:02:17Z","timestamp":1721156537000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Epidermal growth factor-like domain 7 drives brain lymphatic endothelial cell development through integrin \u03b1v\u03b23"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4051-4739","authenticated-orcid":false,"given":"Jingying","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fujuan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianbo","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Cang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4714-9169","authenticated-orcid":false,"given":"Lingfei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"50389_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.cell.2020.06.039","volume":"182","author":"G Oliver","year":"2020","unstructured":"Oliver, G., Kipnis, J., Randolph, G. J. & Harvey, N. L. The Lymphatic Vasculature in the 21(st) Century: Novel Functional Roles in Homeostasis and Disease. Cell 182, 270\u2013296 (2020).","journal-title":"Cell"},{"key":"50389_CR2","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1093\/emboj\/21.7.1505","volume":"21","author":"JT Wigle","year":"2002","unstructured":"Wigle, J. T. et al. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. Embo J. 21, 1505\u20131513 (2002).","journal-title":"Embo J."},{"key":"50389_CR3","doi-asserted-by":"publisher","first-page":"3282","DOI":"10.1101\/gad.1727208","volume":"22","author":"NC Johnson","year":"2008","unstructured":"Johnson, N. C. et al. Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes Dev. 22, 3282\u20133291 (2008).","journal-title":"Genes Dev."},{"key":"50389_CR4","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/ni1013","volume":"5","author":"MJ Karkkainen","year":"2004","unstructured":"Karkkainen, M. J. et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat. Immunol. 5, 74\u201380 (2004).","journal-title":"Nat. Immunol."},{"key":"50389_CR5","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/ng.321","volume":"41","author":"BM Hogan","year":"2009","unstructured":"Hogan, B. M. et al. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat. Genet 41, 396\u2013398 (2009).","journal-title":"Nat. Genet"},{"key":"50389_CR6","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1242\/dev.100495","volume":"141","author":"L Le Guen","year":"2014","unstructured":"Le Guen, L. et al. Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis. Development 141, 1239\u20131249 (2014).","journal-title":"Development"},{"key":"50389_CR7","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1161\/CIRCULATIONAHA.113.002779","volume":"129","author":"M Jeltsch","year":"2014","unstructured":"Jeltsch, M. et al. CCBE1 enhances lymphangiogenesis via a disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation. Circulation 129, 1962\u20131971 (2014).","journal-title":"Circulation"},{"key":"50389_CR8","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/emboj.2011.456","volume":"31","author":"L Planas-Paz","year":"2012","unstructured":"Planas-Paz, L. et al. Mechanoinduction of lymph vessel expansion. Embo J. 31, 788\u2013804 (2012).","journal-title":"Embo J."},{"key":"50389_CR9","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1161\/CIRCRESAHA.109.206326","volume":"106","author":"F Galvagni","year":"2010","unstructured":"Galvagni, F. et al. Endothelial Cell Adhesion to the Extracellular Matrix Induces c-Src-Dependent VEGFR-3 Phosphorylation Without the Activation of the Receptor Intrinsic Kinase Activity. Circulation Res. 106, 1839\u2013U1125 (2010).","journal-title":"Circulation Res."},{"key":"50389_CR10","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1016\/j.cub.2006.05.026","volume":"16","author":"AM Kuchler","year":"2006","unstructured":"Kuchler, A. M. et al. Development of the zebrafish lymphatic system requires VEGFC signaling. Curr. Biol. 16, 1244\u20131248 (2006).","journal-title":"Curr. Biol."},{"key":"50389_CR11","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/nm1427","volume":"12","author":"K Yaniv","year":"2006","unstructured":"Yaniv, K. et al. Live imaging of lymphatic development in the zebrafish. Nat. Med 12, 711\u2013716 (2006).","journal-title":"Nat. Med"},{"key":"50389_CR12","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1242\/dev.089565","volume":"140","author":"K Koltowska","year":"2013","unstructured":"Koltowska, K., Betterman, K. L., Harvey, N. L. & Hogan, B. M. Getting out and about: the emergence and morphogenesis of the vertebrate lymphatic vasculature. Development 140, 1857\u20131870 (2013).","journal-title":"Development"},{"key":"50389_CR13","doi-asserted-by":"publisher","first-page":"e47079","DOI":"10.15252\/embr.201847079","volume":"20","author":"TC Eng","year":"2019","unstructured":"Eng, T. C. et al. Zebrafish facial lymphatics develop through sequential addition of venous and non-venous progenitors. EMBO Rep. 20, e47079 (2019).","journal-title":"EMBO Rep."},{"key":"50389_CR14","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.1242\/dev.077701","volume":"139","author":"KS Okuda","year":"2012","unstructured":"Okuda, K. S. et al. lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish. Development 139, 2381\u20132391 (2012).","journal-title":"Development"},{"key":"50389_CR15","doi-asserted-by":"publisher","first-page":"e25932","DOI":"10.7554\/eLife.25932","volume":"6","author":"M van Lessen","year":"2017","unstructured":"van Lessen, M. et al. Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development. Elife 6, e25932 (2017).","journal-title":"Elife"},{"key":"50389_CR16","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/nn.4558","volume":"20","author":"NI Bower","year":"2017","unstructured":"Bower, N. I. et al. Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish. Nat. Neurosci. 20, 774\u2013783 (2017).","journal-title":"Nat. Neurosci."},{"key":"50389_CR17","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/s00401-019-02091-z","volume":"139","author":"S Shibata-Germanos","year":"2020","unstructured":"Shibata-Germanos, S. et al. Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges. Acta Neuropathol. 139, 383\u2013401 (2020).","journal-title":"Acta Neuropathol."},{"key":"50389_CR18","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1161\/CIRCRESAHA.120.317372","volume":"128","author":"D Castranova","year":"2021","unstructured":"Castranova, D. et al. Live Imaging of Intracranial Lymphatics in the Zebrafish. Circ. Res 128, 42\u201358 (2021).","journal-title":"Circ. Res"},{"key":"50389_CR19","doi-asserted-by":"publisher","first-page":"dev200729","DOI":"10.1242\/dev.200729","volume":"149","author":"J Chen","year":"2022","unstructured":"Chen, J., He, J. & Luo, L. Brain vascular damage-induced lymphatic ingrowth is directed by Cxcl12b\/Cxcr4a. Development 149, dev200729 (2022).","journal-title":"Development"},{"key":"50389_CR20","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.devcel.2019.03.022","volume":"49","author":"J Chen","year":"2019","unstructured":"Chen, J. et al. Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish. Dev. Cell 49, 697\u2013710 e695 (2019).","journal-title":"Dev. Cell"},{"key":"50389_CR21","doi-asserted-by":"publisher","first-page":"3115","DOI":"10.1016\/j.devcel.2021.09.005","volume":"56","author":"J Chen","year":"2021","unstructured":"Chen, J. et al. Acute brain vascular regeneration occurs via lymphatic transdifferentiation. Dev. Cell 56, 3115\u2013313127 e3116 (2021).","journal-title":"Dev. Cell"},{"key":"50389_CR22","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1182\/blood-2011-10-322446","volume":"119","author":"D Nichol","year":"2012","unstructured":"Nichol, D. & Stuhlmann, H. EGFL7: a unique angiogenic signaling factor in vascular development and disease. Blood 119, 1345\u20131352 (2012).","journal-title":"Blood"},{"key":"50389_CR23","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/dvdy.20063","volume":"230","author":"MJ Fitch","year":"2004","unstructured":"Fitch, M. J., Campagnolo, L., Kuhnert, F. & Stuhlmann, H. Egfl7, a novel epidermal growth factor-domain gene expressed in endothelial cells. Dev. Dyn. 230, 316\u2013324 (2004).","journal-title":"Dev. Dyn."},{"key":"50389_CR24","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1182\/blood-2011-11-394882","volume":"121","author":"I Nikolic","year":"2013","unstructured":"Nikolic, I. et al. EGFL7 ligates alphavbeta3 integrin to enhance vessel formation. Blood 121, 3041\u20133050 (2013).","journal-title":"Blood"},{"key":"50389_CR25","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/nature02416","volume":"428","author":"LH Parker","year":"2004","unstructured":"Parker, L. H. et al. The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature 428, 754\u2013758 (2004).","journal-title":"Nature"},{"key":"50389_CR26","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.devcel.2013.03.003","volume":"25","author":"MS Charpentier","year":"2013","unstructured":"Charpentier, M. S. et al. CASZ1 promotes vascular assembly and morphogenesis through the direct regulation of an EGFL7\/RhoA-mediated pathway. Dev. Cell 25, 132\u2013143 (2013).","journal-title":"Dev. Cell"},{"key":"50389_CR27","doi-asserted-by":"publisher","first-page":"6133","DOI":"10.1182\/blood-2010-03-274860","volume":"116","author":"D Nichol","year":"2010","unstructured":"Nichol, D. et al. Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7. Blood 116, 6133\u20136143 (2010).","journal-title":"Blood"},{"key":"50389_CR28","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.1242\/dev.029736","volume":"135","author":"F Kuhnert","year":"2008","unstructured":"Kuhnert, F. et al. Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development 135, 3989\u20133993 (2008).","journal-title":"Development"},{"key":"50389_CR29","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nature14580","volume":"524","author":"A Rossi","year":"2015","unstructured":"Rossi, A. et al. Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524, 230\u2013233 (2015).","journal-title":"Nature"},{"key":"50389_CR30","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/sj.jcbfm.9600408","volume":"27","author":"M Gustavsson","year":"2007","unstructured":"Gustavsson, M. et al. Vascular response to hypoxic preconditioning in the immature brain. J. Cereb. Blood Flow. Metab. 27, 928\u2013938 (2007).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"50389_CR31","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1002\/hep.23197","volume":"50","author":"F Wu","year":"2009","unstructured":"Wu, F. et al. Novel role for epidermal growth factor-like domain 7 in metastasis of human hepatocellular carcinoma. Hepatology 50, 1839\u20131850 (2009).","journal-title":"Hepatology"},{"key":"50389_CR32","doi-asserted-by":"publisher","first-page":"8526","DOI":"10.1002\/jcp.26792","volume":"233","author":"G Hong","year":"2018","unstructured":"Hong, G. et al. EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis. J. Cell Physiol. 233, 8526\u20138537 (2018).","journal-title":"J. Cell Physiol."},{"key":"50389_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03186-z","volume":"9","author":"C Larochelle","year":"2018","unstructured":"Larochelle, C. et al. EGFL7 reduces CNS inflammation in mouse. Nat. Commun. 9, 819 (2018).","journal-title":"Nat. Commun."},{"key":"50389_CR34","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1242\/dev.105031","volume":"141","author":"A van Impel","year":"2014","unstructured":"van Impel, A. et al. Divergence of zebrafish and mouse lymphatic cell fate specification pathways. Development 141, 1228\u20131238 (2014).","journal-title":"Development"},{"key":"50389_CR35","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.devcel.2008.07.008","volume":"15","author":"JE Fish","year":"2008","unstructured":"Fish, J. E. et al. MiR-126 regulates angiogenic signaling and vascular integrity. Dev.Cell 15, 272\u2013284 (2008).","journal-title":"Dev.Cell"},{"key":"50389_CR36","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.ydbio.2018.03.006","volume":"437","author":"Z Kontarakis","year":"2018","unstructured":"Kontarakis, Z., Rossi, A., Ramas, S., Dellinger, M. T. & Stainier, D. Y. R. Mir-126 is a conserved modulator of lymphatic development. Dev. Biol. 437, 120\u2013130 (2018).","journal-title":"Dev. Biol."},{"key":"50389_CR37","doi-asserted-by":"publisher","first-page":"e24369","DOI":"10.7554\/eLife.24369","volume":"6","author":"M Venero Galanternik","year":"2017","unstructured":"Venero Galanternik, M. et al. A novel perivascular cell population in the zebrafish brain. Elife 6, e24369 (2017).","journal-title":"Elife"},{"key":"50389_CR38","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1242\/dev.048207","volume":"137","author":"J Bussmann","year":"2010","unstructured":"Bussmann, J. et al. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk. Development 137, 2653\u20132657 (2010).","journal-title":"Development"},{"key":"50389_CR39","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.devcel.2012.01.011","volume":"22","author":"YR Cha","year":"2012","unstructured":"Cha, Y. R. et al. Chemokine signaling directs trunk lymphatic network formation along the preexisting blood vasculature. Dev. Cell 22, 824\u2013836 (2012).","journal-title":"Dev. Cell"},{"key":"50389_CR40","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1016\/j.celrep.2015.10.055","volume":"13","author":"K Koltowska","year":"2015","unstructured":"Koltowska, K. et al. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish. Cell Rep. 13, 1828\u20131841 (2015).","journal-title":"Cell Rep."},{"key":"50389_CR41","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/jcp.20106","volume":"202","author":"X Zhang","year":"2005","unstructured":"Zhang, X., Groopman, J. E. & Wang, J. F. Extracellular matrix regulates endothelial functions through interaction of VEGFR-3 and integrin alpha5beta1. J. Cell Physiol. 202, 205\u2013214 (2005).","journal-title":"J. Cell Physiol."},{"key":"50389_CR42","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.1158\/0008-5472.CAN-09-3761","volume":"70","author":"B Garmy-Susini","year":"2010","unstructured":"Garmy-Susini, B. et al. Integrin alpha4beta1 signaling is required for lymphangiogenesis and tumor metastasis. Cancer Res. 70, 3042\u20133051 (2010).","journal-title":"Cancer Res."},{"key":"50389_CR43","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1177\/0271678X19880161","volume":"40","author":"DN Edwards","year":"2020","unstructured":"Edwards, D. N. et al. Integrin \u03b15\u03b21 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke. J. Cereb. Blood Flow. Metab. 40, 1695\u20131708 (2020).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"50389_CR44","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41586-018-0709-7","volume":"564","author":"D Li","year":"2018","unstructured":"Li, D. et al. VCAM-1(+) macrophages guide the homing of HSPCs to a vascular niche. Nature 564, 119\u2013124 (2018).","journal-title":"Nature"},{"key":"50389_CR45","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.585778","volume":"12","author":"Y Li","year":"2021","unstructured":"Li, Y. et al. Antagonizing \u03b1v\u03b23 Integrin Improves Ischemia-Mediated Vascular Normalization and Blood Perfusion by Altering Macrophages. Front Pharm. 12, 585778 (2021).","journal-title":"Front Pharm."},{"key":"50389_CR46","doi-asserted-by":"publisher","first-page":"4557","DOI":"10.1080\/21655979.2022.2029236","volume":"13","author":"X Pan","year":"2022","unstructured":"Pan, X. et al. Cilengitide, an \u03b1v\u03b23-integrin inhibitor, enhances the efficacy of anti-programmed cell death-1 therapy in a murine melanoma model. Bioengineered 13, 4557\u20134572 (2022).","journal-title":"Bioengineered"},{"key":"50389_CR47","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/cr.2015.35","volume":"25","author":"L Long","year":"2015","unstructured":"Long, L. et al. Regulation of transcriptionally active genes via the catalytically inactive Cas9 in C. elegans and D. rerio. Cell Res. 25, 638\u2013641 (2015).","journal-title":"Cell Res."},{"key":"50389_CR48","doi-asserted-by":"publisher","first-page":"e99322","DOI":"10.15252\/embj.201899322","volume":"38","author":"S Urner","year":"2019","unstructured":"Urner, S. et al. Identification of ILK as a critical regulator of VEGFR3 signalling and lymphatic vascular growth. Embo J. 38, e99322 (2019).","journal-title":"Embo J"},{"key":"50389_CR49","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1161\/CIRCULATIONAHA.107.689984","volume":"116","author":"R Knoll","year":"2007","unstructured":"Knoll, R. et al. Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation 116, 515\u2013525 (2007).","journal-title":"Circulation"},{"key":"50389_CR50","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1242\/dev.002576","volume":"134","author":"M Schmidt","year":"2007","unstructured":"Schmidt, M. et al. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development 134, 2913\u20132923 (2007).","journal-title":"Development"},{"key":"50389_CR51","first-page":"2469","volume":"144","author":"LA Lacko","year":"2017","unstructured":"Lacko, L. A. et al. Altered feto-placental vascularization, feto-placental malperfusion and fetal growth restriction in mice with Egfl7 loss of function. Development 144, 2469\u20132479 (2017).","journal-title":"Development"},{"key":"50389_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08163-0","volume":"10","author":"M Hsu","year":"2019","unstructured":"Hsu, M. et al. Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells. Nat. Commun. 10, 229 (2019).","journal-title":"Nat. Commun."},{"key":"50389_CR53","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.1002\/hep.32076","volume":"74","author":"P Cai","year":"2021","unstructured":"Cai, P. et al. Farnesoid X Receptor Is Required for the Redifferentiation of Bipotential Progenitor Cells During Biliary-Mediated Zebrafish Liver Regeneration. Hepatology 74, 3345\u20133361 (2021).","journal-title":"Hepatology"},{"key":"50389_CR54","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/cr.2013.45","volume":"23","author":"N Chang","year":"2013","unstructured":"Chang, N. et al. Genome editing with RNA-guided Cas9 nuclease in zebrafish embryos. Cell Res. 23, 465\u2013472 (2013).","journal-title":"Cell Res."},{"key":"50389_CR55","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1161\/CIRCRESAHA.110.225045","volume":"108","author":"J Zou","year":"2011","unstructured":"Zou, J. et al. Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish. Circ. Res. 108, 201\u2013209 (2011).","journal-title":"Circ. Res."},{"key":"50389_CR56","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.devcel.2013.01.021","volume":"24","author":"H Lu","year":"2013","unstructured":"Lu, H., Ma, J., Yang, Y., Shi, W. & Luo, L. EpCAM is an endoderm-specific Wnt derepressor that licenses hepatic development. Dev. Cell 24, 543\u2013553 (2013).","journal-title":"Dev. Cell"},{"key":"50389_CR57","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1002\/hep.30790","volume":"70","author":"J He","year":"2019","unstructured":"He, J. et al. Mammalian Target of Rapamycin Complex 1 Signaling Is Required for the Dedifferentiation From Biliary Cell to Bipotential Progenitor Cell in Zebrafish Liver Regeneration. Hepatology 70, 2092\u20132106 (2019).","journal-title":"Hepatology"},{"key":"50389_CR58","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1053\/j.gastro.2013.11.045","volume":"146","author":"J He","year":"2014","unstructured":"He, J., Lu, H., Zou, Q. & Luo, L. Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish. Gastroenterology 146, 789\u2013800.e788 (2014).","journal-title":"Gastroenterology"},{"key":"50389_CR59","doi-asserted-by":"publisher","first-page":"3361","DOI":"10.1038\/s41596-020-0376-7","volume":"15","author":"J He","year":"2020","unstructured":"He, J., Mo, D., Chen, J. & Luo, L. Combined whole-mount fluorescence in situ hybridization and antibody staining in zebrafish embryos and larvae. Nat. Protoc. 15, 3361\u20133379 (2020).","journal-title":"Nat. Protoc."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-50389-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-50389-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-50389-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T20:21:57Z","timestamp":1721161317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-50389-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["50389"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-50389-8","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,16]]},"assertion":[{"value":"16 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5986"}}