THE WINGED-HELIX TRANSCRIPTION FACTOR HNF-3-BETA IS REQUIRED FOR NOTOCHORD DEVELOPMENT IN THE MOUSE EMBRYO

HNF-3 beta, a transcription factor of the winged-helix family, is expr essed in embryonic and adult endoderm and also in midline cells of the node, notochord, and floor plate in mouse embryos. To define the func tion of HNF-3 beta a targeted mutation in the HNF 3P locus was generat ed by homologous recombination in embryonic stem cells. Mice lacking H NF-3 beta die by embryonic day (6) 10-11. Mutant embryos examined from E6.5 to E9.5 do not form a distinct node and lack a notochord. In add ition, mutant embryos show marked defects in the organization of somit es and neural tube that may result from the absence of the notochord. The neural tube of mutant embryos exhibits overt anteroposterior polar ity but lacks a floor plate and motor neurons. Endodermal cells are pr esent but fail to form a gut tube in mutant embryos. These studies ind icate that HNF-3 beta has an essential role in the development of axia l mesoderm in mouse embryos.