O6. Cell fate specification in the zebrafish myotome: A paradigm for cross-talk between the Hedgehog and BMP signalling pathways

Abstract

The morphogen like properties of Hedgehog (Hh) family proteins have been well documented in a number of contexts. In vertebrates, the best characterized example of such a role is in the developing neural tube, where different ventral neuronal identities are specified in response to the strength and duration of Shh signaling emanating from the notochord and floorplate. In an analogous fashion, members of the BMP family secreted by the lateral non neural ectoderm and the roofplate of the neural tube act to specify dorsal neural cell fates. The effects of Shh and BMP on cell fate specification in the neural tube are mutually antagonistic but how cells integrate the effects of these opposing influences is not well understood. Several lines of evidence have shown that the specification of distinct cell types in the zebrafish myotome is similarly mediated by varying levels of Hh signalling activity, and that BMP likely plays a role in modulating the response of these cells to Hh activity. Through analysis of the regulation of the eng2a gene, a key marker of muscle cell types induced in response to high threshold levels of Shh, we have now identified a clear link between BMP signaling and expression of a putative Hh target gene. We show that Smad activity represses eng2a expression and that activated forms of Smads bind to specific Hh responsive enhancer elements upstream of the eng2a promoter: moreover, we show that nuclear accumulation of pSmads is abrogated in cells exposed to the highest levels of Hh signaling activity. Our findings provide a mechanistic basis for the response of cells to different levels of a morphogen (Shh) while at the same time revealing a novel example of “cross-talk” between the two signaling pathways.