casanova plays an early and essential role in endoderm formation in zebrafish

The cellular and molecular mechanisms that regulate endoderm development in vertebrates have only recently begun to be explored. Here we show that the zebrafish locus casanova plays an early and essential role in this process . casanova mutants lack a gut tube and do not express any molecular markers of endoderm differentiation. The early endodermal expression of genes such as axial, gata5, and fkd2 does not initiate in casanova mutants, indicatin g that the endoderm is defective from the onset of gastrulation. Mosaic ana lysis demonstrates that casanova functions cell autonomously within the end odermal progenitors. We also report the isolation of a zebrafish homologue of Mixer, a gene important for early endoderm formation in Xenopus. casanov a does not encode zebrafish Mixer, and mixer expression is normal in casano va mutants, indicating that casanova acts downstream of, or parallel to, mi xer to promote endoderm formation. We further find that the forerunner cell s, a specialized group of noninvoluting dorsal mesendodermal cells, do not form in casanova mutants. Studies of casanova mutants do not support an imp ortant role for the forerunner cells in either dorsal axis or tail developm ent, as has been previously proposed. In addition, although different popul ations of mesodermal precursors are generated normally in casanova mutants, morphogenetic defects in the heart, vasculature, blood, and kidney are app arent, suggesting a possible role for the endoderm in morphogenesis of thes e organs. (C) 1999 Academic Press.