Skeletal muscles exhibit notable morphological diversity, yet the developmental mechanisms specifying distinct identities are unclear. Using Drosophila leg muscles, we show that naïve mesodermal precursors undergo stepwise specification orchestrated by epithelial morphogens. Wg/Wnt1 and Dpp/BMP first restrict multipotent precursors into proximal and distal lineages. Within the distal lineage, successive fate bifurcations generate distinct muscle subtypes and a separate nonmuscle lineage of neuronal lamella cells. Focusing on one lineage, we demonstrate that Wg and Dpp act again to control the spatiotemporal deployment of transcription factors, ensuring that groups of myoblasts destined to fuse to produce a specific muscle share a coordinated transcriptional identity. Thus, epithelial morphogens not only pattern the epithelium but also synchronize myoblast specification, enabling the emergence of diverse muscles from syncytial fibers. Our findings provide a framework for the developmental and evolutionary origins of appendicular muscles and may help explain the selective vulnerability of specific muscles in muscular dystrophies.
Guillermin et al. (Wed,) studied this question.