Fgf-driven Tbx protein activities directly induce myf5 and myod to initiate zebrafish myogenesis

Abstract

AbstractSkeletal muscle derives from dorsal mesoderm that is formed during vertebrate gastrulation. Fibroblast growth factor (Fgf) signalling is known to cooperate with transcription factors of the Tbx family to promote dorsal mesoderm formation, but the role of these proteins in skeletal myogenesis has been unclear. Using the zebrafish, we show that dorsally-derived Fgf signals act through Tbx16 and Tbxta to induce two populations of slow and fast trunk muscle precursors at distinct dorsoventral positions. Tbx16 binds to and directly activates the myf5 and myod genes that are required for commitment to skeletal myogenesis. Tbx16 activity depends on Fgf signalling from the organiser. In contrast, Tbxta is not required for myf5 expression. However, Tbxta binds to a specific site upstream of myod not bound by Tbx16, driving myod expression in the adaxial slow precursors dependent upon Fgf signals, thereby initiating muscle differentiation in the trunk. After gastrulation, when similar muscle cell populations in the post-anal tail are generated from the tailbud, declining Fgf signalling is less effective at initiating adaxial myogenesis, which is instead initiated by Hedgehog signalling from the notochord. Our findings provide insight into the ancestral vertebrate trunk myogenic pattern and how it was co-opted during tail evolution to generate similar muscle by new mechanisms.