Notch signalling acts in postmitotic avian myogenic cells to control MyoD activation

During Drosophila myogenesis, Notch signalling acts at multiple steps of th e muscle differentiation process. In vertebrates, Notch activation has been shown to block MyoD activation and muscle differentiation in vitro, sugges ting that this pathway may act to maintain the cells in an undifferentiated proliferative state. In this paper, we address the role of Notch signallin g in vivo during chick myogenesis. We first demonstrate that the Notch1 rec eptor is expressed in postmitotic cells of the myotome and that the Notch l igands Delta1 and Serrate2 are detected in subsets of differentiating myoge nic cells and are thus in position to signal to Notch1 during myogenic diff erentiation. We also reinvestigate the expression of MyoD and Myf5 during a vian myogenesis, and observe that Myf5 is expressed earlier than MyoD, cons istent with previous results in the mouse. We then show that forced express ion of the Notch ligand, Delta1, during early myogenesis, using a retrovira l system, has no effect on the expression of the early myogenic markers Pax 3 and Myf5, but causes strong down-regulation of MyoD in infected somites. Although Delta1 overexpression results in the complete lack of differentiat ed muscles, detailed examination of the infected embryos shows that initial formation of a myotome is not prevented, indicating that exit from the cel l cycle has not been blocked. These results suggest that Notch signalling a cts in postmitotic myogenic cells to control a critical step of muscle diff erentiation.