Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles

Glenn E. Winnier, Tsutomu Kume, Keyu Deng, Rhonda Rogers, Justin Bundy, Cameron Raines, Michael A. Walter, Brigid L.M. Hogan, Simon J. Conway

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

The murine Mf1 and Mfh1 genes have overlapping patterns of expression in the embryo and encode forkhead/winged helix transcription factors with virtually identical DNA binding domains. Previous studies have shown that Mfh1 null mutants have severe cardiovascular defects, including interruptions and coarctations of the aortic arch and ventricular septal defects (Iida et al., Development 124, 4627-4638, 1997). Here, we show that Mf1(1acz) homozygous null mutants also have a similar spectrum of cardiovascular abnormalities. Moreover, most embryos doubly heterozygous for Mfh1(tm1) and Mf1(1acz) die before birth with interruptions and coarctations of the aortic arch, dysgenesis of the aortic and pulmonary valves, ventricular septal defects, and other cardiac anomalies. This nonallelic noncomplementation and the similar patterns of expression of the two genes in the mesenchyme and endothelial cells of the branchial arches, outflow tract, and heart suggest that Mf1 and Mfh1 play interactive roles in the morphogenesis of the cardiovascular system. Implications for the development of human congenital heart defects are discussed.

Original languageEnglish (US)
Pages (from-to)418-431
Number of pages14
JournalDevelopmental Biology
Volume213
Issue number2
DOIs
StatePublished - Sep 15 1999
Externally publishedYes

Keywords

  • Aortic arch
  • Cardiac failure
  • Forkhead
  • Heart development
  • Mouse embryo
  • Mutation
  • Winged helix

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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