New muscle identity code components identified by TRAP control shape and size of muscle subsets in Drosophila

How the diversification of cell types is regulated during development to generate stereotyped tissue patterns remains a challenging question. Here we applied cell type specific translational profiling (TRAP) approach to identify gene expression signatures underlying the diversification of two muscle subsets in Drosophila. Targeting the Slou-positive muscle population, we identified Ptx1 as a new component of the ventral muscle identity code. We also generated temporal transition profiles of TRAP-enriched genes and found that a set of genes encoding regulators of the actin cytoskeleton fitted a cluster specific for lateral transverse (LT) muscles. Two of them, dCryAB and Gelsolin (Gel), encoding actin-binding sHsp and actin-severing protein respectively, displayed LT muscle prevailing expression positively regulated by LT identity factors Lms and Apterous. In dCryAB-mutant embryos, LT muscle shapes had an irregular appearance, whereas Gel-devoid LTs occasionally developed muscle fibre splitting. Importantly, split LT muscles in Gel mutants were enlarged and bore a greater number of myonuclei, a phenotype phenocopied by overexpression of the duf fusion gene. Muscle fibre splitting is a hallmark of diseased muscle in Duchenne and other muscular dystrophies, but how muscles get split is unknown. Our analyses yield evidence that an excessive myoblast fusion could result in splitting, and suggest a deregulation of fusion machinery in dystrophic muscles. We identify new muscle identity gene Ptx1 and a new class of identity realisator genes including Gel, whose function links muscle identity in Drosophila to dystrophic muscle splitting phenotype in humans.