Requirement of myocardin-related transcription factor-B for remodeling of branchial arch arteries and smooth muscle differentiation

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Abstract

Myocardin and the myocardin-related transcription factors (MRTFs) A and B act as coactivators for serum response factor, which plays a key role in cardiovascular development. To determine the functions of MRTF-B in vivo, we generated MRTF-B mutant mice by targeted inactivation of the MRTF-B gene. We show that mice homozygous for an MRTF-B loss-of-function mutation die during mid-gestation from a spectrum of cardiovascular defects that includes abnormal patterning of the branchial arch arteries, double-outlet right ventricle, ventricular septal defects, and thin-walled myocardium. These abnormalities are accompanied by a failure in differentiation of smooth muscle cells within the branchial arch arteries, which are derived from the neural crest. The phenotype of MRTF-B mutant mice is distinct from that of mice lacking myocardin, revealing unique roles for these serum response factor coactivators in the development of different subsets of smooth muscle cells in vivo.

Original languageEnglish (US)
Pages (from-to)15122-15127
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number42
DOIs
StatePublished - Oct 18 2005

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Keywords

  • Cardiovascular development
  • Congenital heart disease
  • Heart
  • Neural crest

ASJC Scopus subject areas

  • General

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