Signalling networks orchestrating the development of Drosophila indirect flight muscles.

Indirect flight muscles (IFMs) of Drosophila melanogaster are among the most structurally ordered and metabolically demanding tissues in the animal kingdom. Importantly, IFMs comprise two anatomically and mechanistically distinct muscle groups: the dorsal longitudinal muscles (DLMs) and the dorsoventral muscles (DVMs). Their ability to sustain high-frequency, stretch-activated oscillations depends not only on specialised sarcomeric architecture but on multilayered signalling networks that coordinate lineage specification, myoblast proliferation, fibre patterning, mechanotransduction, metabolic adaptation and adult maintenance. Although structural components of IFMs have been extensively characterized, less attention has been given to the signalling axis that integrates developmental cues with post-developmental function. Here, we synthesise current knowledge of the signalling pathways that orchestrate muscle development from embryogenesis through metamorphosis and into adult life. We discuss how canonical pathways, including Notch, Wingless (Wg), Hedgehog (Hh), fibroblast growth factor/Heartless (FGF/Htl), epidermal growth factor (EGF) Ras/MAPK, Rho-family GTPases, integrin complexes, Hippo and Transforming Growth Factor-beta (TGF-β), are repurposed and cross-regulated in the context of the DLMs and DVMs. We further examine how muscle identity genes interface with signalling inputs to define fibre-type specification. Finally, we highlight that mechanical, metabolic and growth-regulatory pathways form an integrated signalling hub that tunes muscle size, power output and endurance. This pathway-centric perspective reframes IFM development as a systems-level template of signal integration and provides a foundation for further understanding of tissue morphogenesis.