DORSAL MIDLINE FATE IN DROSOPHILA EMBRYOS REQUIRES TWISTED GASTRULATION, A GENE ENCODING A SECRETED PROTEIN RELATED TO HUMAN CONNECTIVE-TISSUE GROWTH-FACTOR

The twisted gastrulation (tsg) gene is one of seven known zygotic gene s that specify the fate of dorsal cells in Drosophila embryos. Mutatio ns in these genes cause at least some of the cells on the dorsal half of the embryo to adopt more ventral cell fates leading to the proposal that most of these genes participate in establishing, maintaining, or modulating a gradient of a single signaling molecule DECAPENTAPLEGIC (DPP). We have examined the effects of tsg mutations on the developmen t of cuticule elements, expression of a region specific enhancer trap, and patterns of mitotic domains. Mutations of tsg only affect the fat e of a narrow strip of dorsal midline cells and do not affect dorsal e ctoderm cells. However, the pattern of tsg expression is not coinciden t with the territories affected by tsg mutations. Structural analysis of the tsg gene reveals features of a secreted protein suggesting an e xtracellular site of action. The TSG protein bears a weak resemblance to human connective tissue growth factor (CTGF), a TGF-beta-induced pr otein. We propose that dorsal midline cell fate is specified by the co mbination of both a TSG and a DPP signal to which the dorsal midline c ells are uniquely competent to respond.