Dataset Information

Pak2a mutations cause cerebral hemorrhage in redhead zebrafish.

ABSTRACT: The zebrafish is a powerful model for studying vascular development, demonstrating remarkable conservation of this process with mammals. Here, we identify a zebrafish mutant, redhead (rhd(mi149)), that exhibits embryonic CNS hemorrhage with intact gross development of the vasculature and normal hemostatic function. We show that the rhd phenotype is caused by a hypomorphic mutation in p21-activated kinase 2a (pak2a). PAK2 is a kinase that acts downstream of the Rho-family GTPases CDC42 and RAC and has been implicated in angiogenesis, regulation of cytoskeletal structure, and endothelial cell migration and contractility among other functions. Correction of the Pak2a-deficient phenotype by Pak2a overexpression depends on kinase activity, implicating Pak2 signaling in the maintenance of vascular integrity. Rescue by an endothelial-specific transgene further suggests that the hemorrhage seen in Pak2a deficiency is the result of an autonomous endothelial cell defect. Reduced expression of another PAK2 ortholog, pak2b, in Pak2a-deficient embryos results in a more severe hemorrhagic phenotype, consistent with partially overlapping functions for these two orthologs. These data provide in vivo evidence for a critical function of Pak2 in vascular integrity and demonstrate a severe disease phenotype resulting from loss of Pak2 function.

SUBMITTER: Buchner DA

PROVIDER: S-EPMC1955825 | biostudies-other | 2007 Aug

REPOSITORIES: biostudies-other

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pak2a mutations cause cerebral hemorrhage in redhead zebrafish.

Buchner David A DA Su Fengyun F Yamaoka Jennifer S JS Kamei Makoto M Shavit Jordan A JA Barthel Linda K LK McGee Beth B Amigo Julio D JD Kim Seongcheol S Hanosh Andrew W AW Jagadeeswaran Pudur P Goldman Daniel D Lawson Nathan D ND Raymond Pamela A PA Weinstein Brant M BM Ginsburg David D Lyons Susan E SE

Proceedings of the National Academy of Sciences of the United States of America 20070822 35

The zebrafish is a powerful model for studying vascular development, demonstrating remarkable conservation of this process with mammals. Here, we identify a zebrafish mutant, redhead (rhd(mi149)), that exhibits embryonic CNS hemorrhage with intact gross development of the vasculature and normal hemostatic function. We show that the rhd phenotype is caused by a hypomorphic mutation in p21-activated kinase 2a (pak2a). PAK2 is a kinase that acts downstream of the Rho-family GTPases CDC42 and RAC an ...[more]

PMID: 17715297

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Dataset Information

Pak2a mutations cause cerebral hemorrhage in redhead zebrafish.

Publications

pak2a mutations cause cerebral hemorrhage in redhead zebrafish.

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