{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:54:28Z","timestamp":1792450468914,"version":"4.5.0"},"reference-count":57,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS087635"],"award-info":[{"award-number":["R01NS087635"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP180220"],"award-info":[{"award-number":["RP180220"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The central nervous system (CNS) contains a complex network of blood vessels that promote normal tissue development and physiology. Abnormal control of blood vessel morphogenesis and maturation is linked to the pathogenesis of various neurodevelopmental diseases. The CNS-specific genes that regulate blood vessel morphogenesis in development and disease remain largely unknown. Here, we have characterized functions for the prion protein two gene (Prnd) in CNS blood vessel development and physiology. Prnd encodes the glycosylphosphatidylinositol (GPI)-linked protein Doppel, which is expressed on the surface of angiogenic vascular endothelial cells, but is absent in quiescent endothelial cells of the adult CNS. During CNS vascular development, Doppel interacts with receptor tyrosine kinases and activates cytoplasmic signaling pathways involved in endothelial cell survival, metabolism and migration. Analysis of mice genetically null for Prnd reveal impaired CNS blood vessel morphogenesis and associated endothelial cell sprouting defects. Prnd-\/- mice also display defects in endothelial barrier integrity. Collectively, these data reveal novel mechanisms underlying Doppel control of angiogenesis in the developing CNS, and may provide new insights about dysfunctional pathways that cause vascular-related CNS disorders.<\/jats:p>","DOI":"10.1242\/dev.193094","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T21:25:48Z","timestamp":1599513948000},"source":"Crossref","is-referenced-by-count":13,"title":["The vascular endothelial cell-expressed prion protein Prnd\/Doppel promotes angiogenesis and blood-brain barrier development"],"prefix":"10.1242","author":[{"given":"Zhihua","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naze","family":"Avci","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola A.","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je Hoon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Chungbuk National University School of Medicine, Cheongju 361-763, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8345-5478","authenticated-orcid":false,"given":"Joseph H.","family":"McCarty","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas M. D. 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