dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo

The first step in the differentiation of the Drosophila mesoderm is the activation of two regulatory genes, twist [twi) and snail [sna), in ventral regions of early embryos, sna is a transcriptional repressor that is uniformly expressed throughout the presumptive mesoderm. Its sharp lateral limits help to establish the boundary between the mesoderm and neuroectoderm. Genetic studies suggest that sna is a target of the dorsal (dl) morphogen, and this interaction provides a model for determining how a morphogen gradient establishes a sharp, on/off threshold response. We present evidence that dl and twi directly activate sna expression. Site-directed mutagenesis of dl- and twi-binding sites within defined regions of the sna promoter suggest that the two proteins (containing the Rel and helix-loop-helix domains, respectively) function multiplicatively to ensure strong, uniform expression of sna, particularly in ventral-lateral regions where there are diminishing amounts of dl. These results are consistent with the possibility that the sharp sna borders are formed by multiplying the shallow dl gradient and the steeper twi gradient.