Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis

Abstract

Mesenchyme Fork Head-1 (MFH-1) is a forkhead (also called winged helix) transcription factor defined by a common 100-amino acid DNA-binding domain. MFH-1 is expressed in non-notochordal mesoderm in the prospective trunk region and in cephalic neural-crest and cephalic mesoderm-derived mesenchymal cells in the prechordal region of early embryos. Subsequently, strong expression is localized in developing cartilaginous tissues, kidney and dorsal aortas. To investigate the developmental roles of MFH-1 during embryogenesis, mice lacking the MFH-1 locus were generated by targeted mutagenesis. MFH-1-deficient mice died embryonically and perinatally, and exhibited interrupted aortic arch and skeletal defects in the neurocranium and the vertebral column. Interruption of the aortic arch seen in the mutant mice was the same as in human congenital anomalies. These results suggest that MFH-1 has indispensable roles during the extensive remodeling of the aortic arch in neural-crest-derived cells and in skeletogenesis in cells derived from the neural crest and the mesoderm.