Single-cell RNA-Seq of leg disc mesodermal precursors labeled with GFP at five developmental stages
This study investigates how spatial and temporal signaling cues orchestrate the specification of mesodermal progenitors into distinct leg muscle lineages in Drosophila. Using single-cell RNA sequencing across developmental stages, we show that mesodermal precursors initially segregate into central and peripheral populations, defined by specific transcription factor codes such as Lim1, Bi, and Sox100B in central cells, and Hth and Unpg in peripheral cells which prefigure distal and proximal muscle fates, respectively. By computationally and genetically tracking central mesodermal precursors, we demonstrate that these early populations progressively subdivide into distinct muscle lineages, each characterized by unique combinations of transcription factors required for proper muscle development. We further show that the morphogens Wingless (Wg) and Decapentaplegic (Dpp) act in a spatiotemporal manner to control the stepwise evolution of these lineages. By integrating single-cell transcriptomics with spatial mapping and functional genetic analyses, this study establishes that epithelial-derived morphogens coordinate not only epithelial tissue patterning but also the synchronized specification of myoblasts with epithelial patterning, enabling the emergence of diverse leg muscles.