Genetic analysis of dorsoventral pattern formation in the zebrafish: Requirement of a BMP-like ventralizing activity and its dorsal repressor

According to a model based on embryological studies in amphibia, dorsoventral patterning is regulated by the antagonizing function of ventralizing bone morphogenetic proteins (BMPs) and dorsalizing signals generated by Spemann's organizer. Large-scale mutant screens in the zebrafish, Danio rerio, have led to the isolation of two classes of recessive lethal mutations affecting early dorsoventral pattern formation. dine mutant embryos are ventralized, whereas swirl mutants are dorsalized. We show that at early gastrula stages, dine and swirl mutants display an expanded or reduced Bmp4 expression, respectively. The dine and swirl mutant phenotypes both can be phenocopied and rescued by the modulation of BMP signaling in wild-type and mutant embryos. By suppressing BMP signaling in dine mutants, adult fertile dine (-/-) fish were generated. These findings, together with results from the analysis of dino-swirl double mutants, indicate that dine fulfills its dorsalizing activity via a suppression of swirl-dependent, BMP-like ventralizing activities. Finally, cell transplantation experiments show that dine is required on the dorsal side of early gastrula embryos and acts in a non-cell-autonomous fashion. Together, these results provide genetic evidence in support of a mechanism of early dorsoventral patterning that is conserved among vertebrate and invertebrate embryos.