Mesodermal expression of integrin ?5?1 regulates neural crest development and cardiovascular morphogenesis.

ABSTRACT: Integrin ?5-null embryos die in mid-gestation from severe defects in cardiovascular morphogenesis, which stem from defective development of the neural crest, heart and vasculature. To investigate the role of integrin ?5?1 in cardiovascular development, we used the Mesp1(Cre) knock-in strain of mice to ablate integrin ?5 in the anterior mesoderm, which gives rise to all of the cardiac and many of the vascular and muscle lineages in the anterior portion of the embryo. Surprisingly, we found that mutant embryos displayed numerous defects related to the abnormal development of the neural crest such as cleft palate, ventricular septal defect, abnormal development of hypoglossal nerves, and defective remodeling of the aortic arch arteries. We found that defects in arch artery remodeling stem from the role of mesodermal integrin ?5?1 in neural crest proliferation and differentiation into vascular smooth muscle cells, while proliferation of pharyngeal mesoderm and differentiation of mesodermal derivatives into vascular smooth muscle cells was not defective. Taken together our studies demonstrate a requisite role for mesodermal integrin ?5?1 in signaling between the mesoderm and the neural crest, thereby regulating neural crest-dependent morphogenesis of essential embryonic structures.

SUBMITTER: Liang D 

PROVIDER: S-EPMC4252364 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature