Faculty Collaboration Database

Small GTPase Rap1 Is Essential for Mouse Development and Formation of Functional Vasculature. PLoS One 2015;10(12):e0145689

Date

12/30/2015

Pubmed ID

26714318

Pubmed Central ID

PMC4694701

DOI

10.1371/journal.pone.0145689

Scopus ID

2-s2.0-84958225316 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

BACKGROUND: Small GTPase Rap1 has been implicated in a number of basic cellular functions, including cell-cell and cell-matrix adhesion, proliferation and regulation of polarity. Evolutionarily conserved, Rap1 has been studied in model organisms: yeast, Drosophila and mice. Mouse in vivo studies implicate Rap1 in the control of multiple stem cell, leukocyte and vascular cell functions. In vitro, several Rap1 effectors and regulatory mechanisms have been proposed. In particular, Rap1 has been implicated in maintaining epithelial and endothelial cell junction integrity and linked with cerebral cavernous malformations.

RATIONALE: How Rap1 signaling network controls mammalian development is not clear. As a first step in addressing this question, we present phenotypes of murine total and vascular-specific Rap1a, Rap1b and double Rap1a and Rap1b (Rap1) knockout (KO) mice.

RESULTS AND CONCLUSIONS: The majority of total Rap1 KO mice die before E10.5, consistent with the critical role of Rap1 in epithelial morphogenesis. At that time point, about 50% of Tie2-double Rap1 KOs appear grossly normal and develop normal vasculature, while the remaining 50% suffer tissue degeneration and show vascular abnormalities, including hemorrhages and engorgement of perineural vessels, albeit with normal branchial arches. However, no Tie2-double Rap1 KO embryos are present at E15.5, with hemorrhages a likely cause of death. Therefore, at least one Rap1 allele is required for development prior to the formation of the vascular system; and in endothelium-for the life-supporting function of the vasculature.

Author List

Chrzanowska-Wodnicka M, White GC 2nd, Quilliam LA, Whitehead KJ

Authors

Magdalena Chrzanowska PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Gilbert C. White MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Embryo, Mammalian
Endothelial Cells
Gene Knockout Techniques
Hemorrhage
KRIT1 Protein
Mice
Microtubule-Associated Proteins
Neovascularization, Physiologic
Phenotype
Proto-Oncogene Proteins
Signal Transduction
rap GTP-Binding Proteins
rap1 GTP-Binding Proteins