During zebrafish muscle development, Fgf signalling and T-box (Tbx) transcription factors are required for expression of the myogenic regulatory factors (MRFs) myf5 and myod. How these different components interact with each other, however, is not well understood. Now, Simon Hughes and colleagues use gene expression analyses, together with genetic knockout, morpholino knockdown and small-molecule perturbation, to reveal how Fgf signalling and Tbx factors integrate. The authors show that Fgf4, Fgf6a and Fgf8a act together to initiate MRF gene expression in trunk slow-twitch muscle precursors, and MRFs are later maintained and enhanced by Hedgehog (Hh) signalling. Inhibition of Fgf signalling also reduces expression of tbx16 in the trunk, suggesting that is required downstream of Fgf signalling for MRF gene expression. Indeed, chromatin immunoprecipitation and activation of Tbx16 protein without downstream protein synthesis show that Tbx16 binds enhancers of, and directly regulates, the myf5 and myod genes. In the tail, Fgf signalling is dispensable for slow myogenesis, suggesting that during tail evolution different regulatory factors (such as Hh) have been employed. Taken together, these data provide evidence that Fgf signals activate Tbx16 in a feed-forward loop, driving expression of MRFs and subsequent somitic skeletal myogenesis.
Fgf and Tbx muscle in on myogenesis
Fgf and Tbx muscle in on myogenesis. Development 15 April 2020; 147 (8): e0805. doi:
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