{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:01:44Z","timestamp":1792677704734,"version":"4.5.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,8,28]]},"abstract":"<jats:p>\n                    The vasculature tailors to the needs of different tissues and organs. Molecular, structural, and functional specializations are observed in different vascular beds, but few genetic models give insight into how these differences arise. We identify a unique cerebrovascular mutation in the zebrafish affecting the integrity of blood vessels supplying the brain. The zebrafish\n                    <jats:italic>bubblehead<\/jats:italic>\n                    (\n                    <jats:italic>bbh<\/jats:italic>\n                    ) mutant exhibits hydrocephalus and severe cranial hemorrhage during early embryogenesis, whereas blood vessels in other regions of the embryo appear intact. Here we show that hemorrhages are associated with poor cerebral endothelial\u2013mesenchymal contacts and an immature vascular pattern in the head. Positional cloning of bbh reveals a hypomorphic mutation in \u03b2Pix, a binding partner for the p21-activated kinase (Pak) and a guanine nucleotide exchange factor for Rac and Cdc42. \u03b2Pix is broadly expressed during embryonic development and is enriched in the brain and in large blood vessels. By knockdown of specific \u03b2Pix splice variants, we show that they play unique roles in embryonic vascular stabilization or hydrocephalus. Finally, we show that Pak2a signaling is downstream of \u03b2Pix. These data identify an essential\n                    <jats:italic>in vivo<\/jats:italic>\n                    role for \u03b2Pix and Pak2a during embryonic development and illuminate a previously unrecognized pathway specifically involved in cerebrovascular stabilization.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0700825104","type":"journal-article","created":{"date-parts":[[2007,6,16]],"date-time":"2007-06-16T07:57:26Z","timestamp":1181980646000},"page":"13990-13995","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["A \u03b2Pix\u2013Pak2a signaling pathway regulates cerebral vascular stability in zebrafish"],"prefix":"10.1073","volume":"104","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 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Hospital Drive NW, Calgary, AB, Canada T2N 4N1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivera","family":"Starovic-Subota","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie L.","family":"Laliberte","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jau-Nian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Los Angeles, CA 90095; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio 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