{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:19:15Z","timestamp":1790680755048,"version":"4.1.0"},"reference-count":75,"publisher":"The Company of Biologists","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:p>Vascular development of the central nervous system and blood-brain barrier (BBB) induction are closely linked processes. The role of factors that promote endothelial sprouting and vascular leak, such as vascular endothelial growth factor A, are well described, but the factors that suppress angiogenic sprouting and their impact on the BBB are poorly understood. Here, we show that integrin \u03b1V\u03b28 activates angiosuppressive TGF\u03b2 gradients in the brain, which inhibit endothelial cell sprouting. Loss of \u03b1V\u03b28 in the brain or downstream TGF\u03b21-TGFBR2-ALK5-Smad3 signaling in endothelial cells increases vascular sprouting, branching and proliferation, leading to vascular dysplasia and hemorrhage. Importantly, BBB function in Itgb8 mutants is intact during early stages of vascular dysgenesis before hemorrhage. By contrast, Pdgfbret\/ret mice, which exhibit severe BBB disruption and vascular leak due to pericyte deficiency, have comparatively normal vascular morphogenesis and do not exhibit brain hemorrhage. Our data therefore suggest that abnormal vascular sprouting and patterning, not BBB dysfunction, underlie developmental cerebral hemorrhage.<\/jats:p>","DOI":"10.1242\/dev.107193","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T17:08:55Z","timestamp":1416330535000},"page":"4489-4499","source":"Crossref","is-referenced-by-count":103,"title":["Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking \u03b1V\u03b28-TGF\u03b2 signaling in the brain"],"prefix":"10.1242","volume":"141","author":[{"given":"Thomas D.","family":"Arnold","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-177 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Niaudet","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-177 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Fong","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-177 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Siegenthaler","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Gaengel","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-177 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bongnam","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-177 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina M.","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Program, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh-suke","family":"Mukouyama","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell and Neuro-Vascular Biology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Fuxe","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-177 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Akhurst","sequence":"additional","affiliation":[{"name":"Helen Diller Cancer Center and Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christer","family":"Betsholtz","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-177 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Sheppard","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis F.","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Program, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042607514138700_DEV107193C1","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1172\/JCI200318549","article-title":"Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors","volume":"112","author":"Abramsson","year":"2003","journal-title":"J. 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