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Abstract
A combinatorial code of identity transcription factors (iTFs) specifies the diversity of muscle types in Drosophila. We previously showed that two iTFs, Lms and Ap, play critical role in the identity of a subset of larval body wall muscles, the lateral transverse (LT) muscles. Intriguingly, a small portion of ap and lms mutants displays an increased number of LT muscles, a phenotype that recalls pathological split muscle fibers in human. However, genes acting downstream of Ap and Lms to prevent these aberrant muscle feature are not known. Here, we applied a cell type specific translational profiling (TRAP) to identify gene expression signatures underlying identity of muscle subsets including the LT muscles. We found that Gelsolin (Gel) and dCryAB, both encoding actin-interacting proteins, displayed LT muscle prevailing expression positively regulated by, the LT iTFs. Loss of dCryAB function resulted in LTs with irregular shape and occasional branched ends also observed in ap and lms mutant contexts. In contrast, enlarged and then split LTs with a greater number of myonuclei formed in Gel mutants while Gel gain of function resulted in unfused myoblasts, collectively indicating that Gel regulates LTs size and prevents splitting by limiting myoblast fusion. Thus, dCryAB and Gel act downstream of Lms and Ap and contribute to preventing LT muscle branching and splitting. Our findings offer first clues to still unknown mechanisms of pathological muscle splitting commonly detected in human dystrophic muscles and causing muscle weakness.
Highlights
Diversification of cell types is a fundamental process during the development of multicellular organisms and is essential in building functional organs
The muscle network in Drosophila embryos, composed of 30 muscle fibres per abdominal hemisegment, offers a tractable system for studying cell diversification. Despite common characteristics such as formation by myoblast fusion and the capacity to contract, each embryonic Drosophila muscle has a specific size, orientation, number of nuclei, attachment and innervation[1]. How these features are acquired at the muscle-specific level remains unclear, it is generally a ccepted[2,3] that the muscle founder cells (FCs), which are at the origin of muscle fibres, harbour all the information required for individual muscle identity
Respective Tr1 and Tr2 fold changes are indicated on the heatmap. (H) In situ hybridisation showing that Gel and dCryAB that are part of the “actin binding” GO class are predominantly expressed in lateral transverse (LT) muscles
Summary
Diversification of cell types is a fundamental process during the development of multicellular organisms and is essential in building functional organs. Despite common characteristics such as formation by myoblast fusion and the capacity to contract, each embryonic Drosophila muscle has a specific size, orientation, number of nuclei, attachment and innervation[1] How these features are acquired at the muscle-specific level remains unclear, it is generally a ccepted[2,3] that the muscle founder cells (FCs), which are at the origin of muscle fibres, harbour all the information required for individual muscle identity. TRAP-purified mRNA profiling followed by bioinformatic analysis and generation of temporal transition profiles identified muscle subset-specific translatome signatures with Gelsolin (Gel) and dCryAB as new identity realisator genes controlling shape- and size-related properties of Lms-expressing muscles. DCryAB and Gel act downstream of Ap and Lms and their loss-of-function phenotypes recall dystrophic muscle branching/splitting in h umans[18]
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