Myotome morphogenesis requires the specification of distinct muscle cell types. In zebrafish, the specification of medial fast-twitch fibres (MFFs) and slow-twitch muscle pioneers (MPs), both of which express engrailed (eng) genes, is regulated by hedgehog (Hh) signalling but the mechanistic basis of this regulation is unclear. On , Philip Ingham and co-workers demonstrate that the eng2a promoter integrates repressive and activating signals from the Bmp and Hh pathways, respectively, to limit its expression to MFFs and MPs during zebrafish myotome development. The researchers identified a minimal element in the eng2a promoter that can drive reporter gene expression specifically in MFFs and MPs. This element binds both Gli2, a mediator of Hh signalling, and activated Smads, mediators of Bmp signalling. They demonstrate that Hh activity antagonises Smad activation in myotomal cells and, conversely, that aberrant Smad activation suppresses eng2a expression. Their studies identify novel crosstalk between the Hh and Bmp pathways that may be mediated by direct interactions between Gli and Smad proteins.
