Dorsal-ventral patterning of the zebrafish embryo

Three zebrafish mutants, swirl ( swr), somitabun (sbn), and snailhouse (snh), which exhibit dorsalized phenotypes, have been identified (Mullins et al., 1996). The genes corresponding to these mutants, bmp2b/swr, smad5/ sbn, and bmp7/snh, are members of a BMP pathway (B. Schmid and M. Mullins; Hild et al., 1999; Schmid et al., 2000). We show that these mutants display alterations in the expression of markers of cells located in dorsal and ventral regions of the early gastrula. We show that the domains of expression of ventral markers are reduced in these mutants, with a concomitant expansion of dorsal markers into ventral areas. These changes in gene expression occur prior to or early in gastrulation, at time periods prior to cell commitment in the zebrafish (Ho and Kimmel, 1993). These results show that the swr/bmp2b, sbn/smad5, and snh/bmp7 genes are required for early dorsal-ventral (DV) pattern formation of the zebrafish embryo. We also examined markers of ectoderm cells derived from lateral areas of the fate map. We found that many of these markers, and specifically markers of cranial neural crest progenitors (CNCP), are particularly sensitive to a reduction in BMP activity, both in the context of these mutants and also in in vivo overexpression studies. We propose that low BMP activity is present in lateral regions of the gastrula, through the interaction of BMP inhibitors from dorsal axial mesoderm and BMPs expressed in ventral regions, and that a low BMP activity level specifies CNCP. Our analysis in these mutants of cell types situated at dorsal and intermediate positions along the DV axis of the spinal cord, another ectodermally-derived structure, also shows a dependence on BMP activity for the development of these cell types. In conclusion, we demonstrate a genetic requirement in the zebrafish for BMP activity in the proper specification of ectodermal tissues derived from ventral and lateral gastrula cell types, including prospective dorsal and intermediate neural cell types of the spinal cord.