Spatio-temporal control of myoblast identity drives muscle diversity in the Drosophila leg

Skeletal muscles display remarkable morphological diversity, but the developmental mechanisms specifying distinct muscle morphology remain poorly understood. Using Drosophila leg muscles as a model, we uncover how naïve mesodermal precursors progressively acquire lineage-restricted identities through a stepwise specification program guided by epithelial morphogens.

Initially, multipotent mesodermal precursors become spatially and transcriptionally restricted into two broad lineages - proximal and distal - under the combined influence of Wg/Wnt1 and Dpp/BMP signals from the overlying epithelium.

By tracing mesodermal precursors that eventually give rise to distal leg muscles, we reveal a second sequence of fate bifurcations that generate distinct muscle subtypes prior to myoblast fusion, as well as a separate lineage producing neuronal lamella cells. Focusing on a single muscle lineage, we show that Wg and Dpp act again during a second phase to control the spatial and temporal deployment of specific transcription factors, ultimately specifying a unique muscle identity.

These findings demonstrate that epithelial morphogens not only pattern the epithelium but also orchestrate muscle diversity by promoting stepwise mesodermal specification. Mesodermal precursors translate morphogen signals over time and space to activate distinct transcriptional programs that operate in parallel with the general program of myogenesis, enabling the emergence of distinct muscle and non- muscle lineages whose unique identities underpin their specialized functions.