goosecoid expression represses Brachyury in embryonic stem cells and affects craniofacial development in chimeric mice

The homeobox gene goosecoid, originally identified in Xenopus, is expressed in the organizer or its equivalent during gastrulation in the frog, chick, zebrafish and mouse. To investigate the role of goosecoid in mouse develop ment, we have generated embryonic stem cells that stably overexpress the mu rine homolog of goosecoid. These cells show a repression of the gastrulatio n-associated gene Brachyury, Interestingly, repression of Brachyury is cons erved between Xenopus and mouse despite the lack of conservation of the Bra chyury promoter. Further characterization of the goosecoid-overexpressing E S cells revealed that they maintain the expression of stage-specific embryo nic antigen-1,and teratomas derived from goosecoid-overexpressing cells sho w the presence of cell types derived from all three germ layers. Some highl y chimeric mice derived from goosecoid-overexpressing cells displayed skull defects. These observations suggest that goosecoid may play a role in spec ification of anterior mesendodermal fates and specifically in mouse craniof acial development.