Coregulation of anterior and posterior mesendodermal development by a hairy-related transcriptional repressor

During embryonic development in vertebrates, the endoderm becomes patterned along the anteroposterior axis to produce distinct derivatives. How this r egulation is controlled is not well understood. We report that the zebrafis h hairy/enhancer of split [E(spI)]-related gene her5 plays a critical role in this process. At gastrulation, following endoderm induction and further cell interaction processes including a local release of Notch/Delta signali ng, her5 expression is progressively excluded from the presumptive anterior - and posteriormost mesendodermal territories to become restricted to an ad jacent subpopulation of dorsal endodermal precursors. Ectopic misexpression s of wild-type and mutant forms of her5 reveal that her5 functions primaril y within the endodermal/endmost mesendodermal germ layer to inhibit cell pa rticipation to the endmost-fated mesendoderm. In this process, her5 acts as an active transcriptional repressor. These features are strikingly reminis cent of the function of Drosophila Hairy/E(spl) factors in cell fate decisi ons. Our results provide the first model for vertebrate endoderm patterning where an early regulatory step at gastrulation, mediated by her5 controls cell contribution jointly to the anterior- and posteriormost mesendodermal regions.