Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis

Dong Liang, Xia Wang, Ashok Mittal, Sonam Dhiman, Shuan Yu Hou, Karl Degenhardt, Sophie Astrof

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Integrin α5-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 α5β1 in cardiovascular development, we used the Mesp1Cre knock-in strain of mice to ablate integrin α5 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 α5β1 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 α5β1 in signaling between the mesoderm and the neural crest, thereby regulating neural crest-dependent morphogenesis of essential embryonic structures.

Original languageEnglish (US)
Pages (from-to)232-244
Number of pages13
JournalDevelopmental Biology
Volume395
Issue number2
DOIs
StatePublished - Nov 15 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Keywords

  • Aortic arch artery development
  • Integrin alpha5
  • Mesoderm
  • Neural crest

Fingerprint

Dive into the research topics of 'Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis'. Together they form a unique fingerprint.

Cite this