Whole-Genome Analysis of Muscle Founder Cells Implicates the Chromatin Regulator Sin3A in Muscle Identity

•Subsets of fly muscle founder cells were purified by FACS and profiled by microarray•A shared set of genes is enriched in two founder cell populations•We identify 11 transcription factors and chromatin regulators with roles in muscle•The chromatin regulator Sin3A fine-tunes muscle response to identity genes

SummarySkeletal muscles are formed in numerous shapes and sizes, and this diversity impacts function and disease susceptibility. To understand how muscle diversity is generated, we performed gene expression profiling of two muscle subsets from Drosophila embryos. By comparing the transcriptional profiles of these subsets, we identified a core group of founder cell-enriched genes. We screened mutants for muscle defects and identified functions for Sin3A and 10 other transcription and chromatin regulators in the Drosophila embryonic somatic musculature. Sin3A is required for the morphogenesis of a muscle subset, and Sin3A mutants display muscle loss and misattachment. Additionally, misexpression of identity gene transcription factors in Sin3A heterozygous embryos leads to direct transformations of one muscle into another, whereas overexpression of Sin3A results in the reverse transformation. Our data implicate Sin3A as a key buffer controlling muscle responsiveness to transcription factors in the formation of muscle identity, thereby generating tissue diversity.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide