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

GE Winnier, T Kume, K Deng, R Rogers, J Bundy… - Developmental …, 1999 - Elsevier
GE Winnier, T Kume, K Deng, R Rogers, J Bundy, C Raines, MA Walter, BLM Hogan
Developmental biology, 1999Elsevier
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 Mf1lacZ
homozygous null mutants also have a similar spectrum of cardiovascular abnormalities …
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 Mf1lacZ homozygous null mutants also have a similar spectrum of cardiovascular abnormalities. Moreover, most embryos doubly heterozygous for Mfh1tm1 and Mf1lacZ 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 thatMf1 and Mfh1 play interactive roles in the morphogenesis of the cardiovascular system. Implications for the development of human congenital heart defects are discussed.
Elsevier