ESSENTIAL ROLES OF THE WINGED HELIX TRANSCRIPTION FACTOR MFH-1 IN AORTIC-ARCH PATTERNING AND SKELETOGENESIS

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 prospect ive trunk region and in cephalic neural-crest and cephalic mesoderm-de rived mesenchymal cells in the prechordal region of early embryos, Sub sequently, strong expression is localized in developing cartilaginous tissues, kidney and dorsal aortas, To investigate the developmental ro les of MFH-1 during embryogenesis, mice lacking the MFH-1 locus were g enerated by targeted mutagenesis, MFH-1-deficient mice died embryonica lly and perinatally, and exhibited interrupted aortic arch and skeleta l defects in the neurocranium and the vertebral column. Interruption o f the aortic arch seen in the mutant mice was the same as in human con genital anomalies. These results suggest that MFH-1 has indispensable roles during the extensive remodeling of the aortic arch in neural-cre st-derived cells and in skeletogenesis in cells derived from the neura l crest and the mesoderm.