{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:29:36Z","timestamp":1768516176564,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,15]]},"group-title":"Developmental Biology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T00:00:00Z","timestamp":1734220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Cerebrovascular endothelial cell (EC) subtypes characterized by blood-brain barrier (BBB) properties or fenestrated pores are essential components of brain-blood interfaces, supporting brain function and homeostasis. To date, the origins and developmental mechanisms underlying this heterogeneous EC network remain largely unclear. Using single-cell-resolution lineage tracing in zebrafish, we discover a multipotent vascular niche at embryonic capillary borders that generates ECs with BBB or fenestrated molecular identity. RNAscope analysis demonstrates restricted expression of\n                  <jats:italic>flt4<\/jats:italic>\n                  in sprouting ECs contributing to fenestrated choroid plexus (CP) vasculature, identifying an early molecular distinction from adjacent BBB vessels. Mechanistically,\n                  <jats:italic>flt4<\/jats:italic>\n                  null and cytoplasmic-domain-deletion mutants exhibit CP vascularization defects when combined with\n                  <jats:italic>vegfr2<\/jats:italic>\n                  zebrafish paralog deletion. Pharmacological results support this co-requirement of Flt4 and Vegfr2 signaling and suggest the PI3K and ERK pathways as downstream effectors. These findings reveal a specialized developmental origin for BBB and fenestrated EC subtypes, and establish Flt4 as a crucial guidance receptor mediating their angiogenic segregation.\n                <\/jats:p>","DOI":"10.1101\/2024.12.10.627641","type":"posted-content","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T12:23:44Z","timestamp":1735734224000},"source":"Crossref","is-referenced-by-count":1,"title":["Angiogenic mechanisms governing the segregation of blood-brain barrier and fenestrated capillaries derived from a multipotent cerebrovascular niche"],"prefix":"10.64898","author":[{"given":"Nathanael J.","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sweta","family":"Parab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda E.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Xiong","family":"Leong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota L.","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025011523550980000_2024.12.10.627641v2.1","first-page":"192","article-title":"Die \u00e4ussere und innere Sekretion des gesunden und kranken Organismus im Lichte der \u2018vitalen F\u00e4rbung","volume":"64","year":"1909","journal-title":"Beitr\u00e4g Klinische Chirurgie"},{"key":"2025011523550980000_2024.12.10.627641v2.2","first-page":"1","article-title":"Vitalf\u00e4rbung am Zentralnervensyatem. 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