RRC ID 75040
著者 Pillay LM, Yano JJ, Davis AE, Butler MG, Ezeude MO, Park JS, Barnes KA, Reyes VL, Castranova D, Gore AV, Swift MR, Iben JR, Kenton MI, Stratman AN, Weinstein BM.
タイトル In vivo dissection of Rhoa function in vascular development using zebrafish.
ジャーナル Angiogenesis
Abstract The small monomeric GTPase RHOA acts as a master regulator of signal transduction cascades by activating effectors of cellular signaling, including the Rho-associated protein kinases ROCK1/2. Previous in vitro cell culture studies suggest that RHOA can regulate many critical aspects of vascular endothelial cell (EC) biology, including focal adhesion, stress fiber formation, and angiogenesis. However, the specific in vivo roles of RHOA during vascular development and homeostasis are still not well understood. In this study, we examine the in vivo functions of RHOA in regulating vascular development and integrity in zebrafish. We use zebrafish RHOA-ortholog (rhoaa) mutants, transgenic embryos expressing wild type, dominant negative, or constitutively active forms of rhoaa in ECs, pharmacological inhibitors of RHOA and ROCK1/2, and Rock1 and Rock2a/b dgRNP-injected zebrafish embryos to study the in vivo consequences of RHOA gain- and loss-of-function in the vascular endothelium. Our findings document roles for RHOA in vascular integrity, developmental angiogenesis, and vascular morphogenesis in vivo, showing that either too much or too little RHOA activity leads to vascular dysfunction.
巻・号 25(3)
ページ 411-434
公開日 2022-8-1
DOI 10.1007/s10456-022-09834-9
PII 10.1007/s10456-022-09834-9
PMID 35320450
MeSH Animals Animals, Genetically Modified Endothelial Cells / metabolism Endothelium, Vascular / metabolism Signal Transduction Zebrafish* / genetics rhoA GTP-Binding Protein* / genetics rhoA GTP-Binding Protein* / metabolism
IF 9.78
リソース情報
ゼブラフィッシュ gSAlzGFFD478A UAS:EGFP