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 language | English (US) |
|---|---|
| Pages (from-to) | 418-431 |
| Number of pages | 14 |
| Journal | Developmental Biology |
| Volume | 213 |
| Issue number | 2 |
| DOIs | |
| State | Published - Sep 15 1999 |
Funding
We thank Drs. Susan Kidson, Joey Barnett, and Scott Baldwin for advice and Drs. Thomas Daniel, Maureen Gannon, and members of the Hogan laboratory for critical reading of the manuscript. S.J.C acknowledges support by NIH Grants HL60714 and HL60104 and a Basil O’Connor Starter Scholar Research Award from the March of Dimes Birth Defects Foundation. G.W. and T.K. were Associates and B.L.M.H. is an Investigator of the Howard Hughes Medical Institute.
Keywords
- Aortic arch
- Cardiac failure
- Forkhead
- Heart development
- Mouse embryo
- Mutation
- Winged helix
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
- Developmental Biology