PUBLICATION

In vivo dissection of Rhoa function in vascular development using zebrafish

Authors
Pillay, L.M., Yano, J.J., Davis, A.E., Butler, M.G., Ezeude, M.O., Park, J.S., Barnes, K.A., Reyes, V.L., Castranova, D., Gore, A.V., Swift, M.R., Iben, J.R., Kenton, M.I., Stratman, A.N., Weinstein, B.M.
ID
ZDB-PUB-220324-10
Date
2022
Source
Angiogenesis   25(3): 411-434 (Journal)
Registered Authors
Butler, Matthew, Castranova, Dan, Davis, Andrew, Gore, Aniket, Pillay, Laura, Stratman, Amber, Swift, Matthew Russell, Weinstein, Brant M.
Keywords
Angiogenesis, Endothelial cell, Hemorrhage, Rhoa, Rock, Zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Endothelial Cells/metabolism
  • Endothelium, Vascular/metabolism
  • Signal Transduction
  • Zebrafish*/genetics
  • rhoA GTP-Binding Protein*/genetics
  • rhoA GTP-Binding Protein*/metabolism
PubMed
35320450 Full text @ 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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes