Intrinsic control of muscle attachment sites matching

How a stereotypic muscle pattern is established, and adapted to fit locomotion behaviour is a fascinating question. Here we set up the targeted deletion of cis-regulatory modules (CRMs) controlling the transcription of Drosophila muscle identity transcription factors (iTF) to generate larval muscle identity mutants. By focusing on one muscle transcription and morphology, we show that selection of muscle attachment sites and the precision of muscle/muscle matching is intrinsic to muscle identity. It involves propagation of the iTF expression code from a founder myoblast to the other syncytial nuclei after fusion. Live imaging indicates that the precise staggered muscle attachment pattern involves attraction to tendon cells and homotypic repulsion. Unbalance leads to the formation of abnormal, branched muscles. Single muscle morphology shifts induce subtle locomotor behaviour. Together this work highlights that CRM deletion is an effective setting for creating muscle-specific defects and branched muscles, as new paradigms to study the development of human myopathies affecting subsets of muscles. Highlights – First muscle-identity mutants, via deletion of specific cis-regulatory modules – Reprogramming of syncytial nuclei is key to muscle morphological identity – Selection of muscle attachment sites; attraction and retraction intrinsic to muscle identity – Genetically controlled formation of branched muscles, a new paradigm for functional studies – Single muscle morphology shift induces subtle locomotor behaviour modification