A βPix–Pak2a signaling pathway regulates cerebral vascular stability in zebrafish
作者： J. Liu , S. D. Fraser , P. W. Faloon , E. L. Rollins , J. Vom Berg
关键词: Positional cloning 、 Cell biology 、 p21-activated kinases 、 Gene knockdown 、 Guanine nucleotide exchange factor 、 Biology 、 Zebrafish 、 Genetic model 、 Mutation 、 Molecular biology 、 Signal transduction
摘要: The vasculature tailors to the needs of different tissues and organs. Molecular, structural, functional specializations are observed in vascular beds, but few genetic models give insight into how these differences arise. We identify a unique cerebrovascular mutation zebrafish affecting integrity blood vessels supplying brain. bubblehead (bbh) mutant exhibits hydrocephalus severe cranial hemorrhage during early embryogenesis, whereas other regions embryo appear intact. Here we show that hemorrhages associated with poor cerebral endothelial–mesenchymal contacts an immature pattern head. Positional cloning bbh reveals hypomorphic βPix, binding partner for p21-activated kinase (Pak) guanine nucleotide exchange factor Rac Cdc42. βPix is broadly expressed embryonic development enriched brain large vessels. By knockdown specific splice variants, they play roles stabilization or hydrocephalus. Finally, Pak2a signaling downstream βPix. These data essential vivo role illuminate previously unrecognized pathway specifically involved stabilization.
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