{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:59:28Z","timestamp":1784555968278,"version":"3.55.0"},"reference-count":78,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["HL006115-14"],"award-info":[{"award-number":["HL006115-14"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:p>\n                    The central nervous system (CNS) parenchyma has conventionally been believed to lack lymphatic vasculature, likely owing to a non-permissive microenvironment that hinders the formation and growth of lymphatic endothelial cells (LECs). Recent findings of ectopic expression of LEC markers including prospero homeobox 1 (PROX1), a master regulator of lymphatic differentiation, and the vascular permeability marker plasmalemma vesicle\u2013associated protein (PLVAP) in certain glioblastomas (GBM) and brain arteriovenous malformations have prompted investigation into their roles in cerebrovascular malformations, tumor environments, and blood-brain barrier (BBB) abnormalities. To explore the relationship between ectopic LEC properties and BBB disruption, we used endothelial cell\u2013specific\n                    <jats:italic>Prox1<\/jats:italic>\n                    overexpression mutants. When induced during embryonic stages of BBB formation, endothelial\n                    <jats:italic>Prox1<\/jats:italic>\n                    expression induces hybrid blood-lymphatic phenotypes in the developing CNS vasculature. This effect is not observed when\n                    <jats:italic>Prox1<\/jats:italic>\n                    is overexpressed during postnatal BBB maturation. Ectopic\n                    <jats:italic>Prox1<\/jats:italic>\n                    expression leads to significant vascular malformations and enhanced vascular leakage, resulting in BBB disruption when induced during both embryonic and postnatal stages. Mechanistically, PROX1 downregulates critical BBB-associated genes, including\n                    <jats:italic>\u03b2<\/jats:italic>\n                    <jats:italic>-catenin<\/jats:italic>\n                    and\n                    <jats:italic>claudin-5<\/jats:italic>\n                    , which are essential for BBB development and maintenance. These findings suggest that PROX1 compromises BBB integrity by negatively regulating BBB-associated gene expression and Wnt\/\u03b2-catenin signaling.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.187716","type":"journal-article","created":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T19:00:49Z","timestamp":1767294049000},"source":"Crossref","is-referenced-by-count":3,"title":["Endothelial PROX1 induces blood-brain barrier disruption in the central nervous system"],"prefix":"10.1172","volume":"11","author":[{"given":"Sara","family":"Gonz\u00e1lez-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Sato","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National 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