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However, how these cellular processes are quantitatively coordinated to drive vascular network morphogenesis remains unknown. Here, using the zebrafish vasculature as a model system, we demonstrate that the balanced distribution of endothelial cells, as well as the resulting regularity of vessel calibre, is a result of cell migration from veins towards arteries and cell proliferation in veins. We identify the Wiskott-Aldrich Syndrome protein (WASp) as an important molecular regulator of this process and show that loss of coordinated migration from veins to arteries upon wasb depletion results in aberrant vessel morphology and the formation of persistent arteriovenous shunts. We demonstrate that WASp achieves its function through the coordination of junctional actin assembly and PECAM1 recruitment and provide evidence that this is conserved in humans. Overall, we demonstrate that functional vascular patterning in the zebrafish trunk is established through differential cell migration regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations.<\/jats:p>","DOI":"10.1242\/dev.200195","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T06:12:48Z","timestamp":1640067168000},"source":"Crossref","is-referenced-by-count":23,"title":["WASp controls oriented migration of endothelial cells to achieve functional vascular patterning"],"prefix":"10.1242","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3179-4160","authenticated-orcid":false,"given":"Andr\u00e9","family":"Rosa","sequence":"first","affiliation":[{"name":"Integrative Vascular Biology Laboratory, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany"},{"name":"DZHK (German Center for Cardiovascular 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1877-2968","authenticated-orcid":false,"given":"Silvanus","family":"Alt","sequence":"additional","affiliation":[{"name":"Integrative Vascular Biology Laboratory, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Berlin 10785, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1164-3322","authenticated-orcid":false,"given":"Alexandra","family":"Klaus-Bergmann","sequence":"additional","affiliation":[{"name":"Integrative Vascular Biology Laboratory, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Berlin 10785, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8586-1605","authenticated-orcid":false,"given":"Lowell T.","family":"Edgar","sequence":"additional","affiliation":[{"name":"Centre for Medical Informatics, Usher Institute, The University of Edinburgh, Edinburgh EH16 4UX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eireen","family":"Bartels-Klein","sequence":"additional","affiliation":[{"name":"Integrative Vascular Biology Laboratory, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Berlin 10785, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1847-4517","authenticated-orcid":false,"given":"Russell T.","family":"Collins","sequence":"additional","affiliation":[{"name":"Integrative Vascular Biology Laboratory, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Berlin 10785, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1741-4106","authenticated-orcid":false,"given":"Anna","family":"Szymborska","sequence":"additional","affiliation":[{"name":"Integrative Vascular Biology Laboratory, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Berlin 10785, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1606-6373","authenticated-orcid":false,"given":"Baptiste","family":"Coxam","sequence":"additional","affiliation":[{"name":"Integrative Vascular Biology Laboratory, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 13125, Germany"},{"name":"DZHK (German 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