A crucial component of the endoderm formation pathway, CASANOVA, is encoded by a novel sox-related gene

casanova (cas) mutant zebrafish embryos lack endoderm and develop cardia bi fida. In a substractive screen for Nodal-responsive genes, we isolated an H MG box-containing gene, 10J3, which is expressed in the endoderm. The cas p henotype is rescued by overexpression of 10J3 and can be mimicked by 10J3-d irected morpholinos. furthermore, we identified a mutation within 10J3 codi ng sequence that cosegregates with the cas phenotype, clearly demonstrating that cas is encoded by 10J3. Epistasis experiments are consistent with an instructive role for cas in endoderm formation downstream of Nodal signals and upstream of sox17. In the absence of cas activity, endoderm progenitors differentiate into mesodermal derivatives. Thus, cas is an HMG box-contain ing gene involved in the fate decision between endoderm and mesoderm that a cts downstream of Nodal signals.