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Correct diversification of cell types during development ensures the formation of functional organs. The evolutionarily conserved homeobox genes from  ladybird/Lbx  family were found to act as cell identity genes in a number of embryonic tissues. A prior genetic analysis showed that during  Drosophila  muscle and heart development  ladybird  is required for the specification of a subset of muscular and cardiac precursors. To learn how  ladybird  genes exert their cell identity functions we performed muscle and heart-targeted genome-wide transcriptional profiling and a chromatin immunoprecipitation (ChIP)-on-chip search for direct Ladybird targets. Our data reveal that  ladybird  not only contributes to the combinatorial code of transcription factors specifying the identity of muscle and cardiac precursors, but also regulates a large number of genes involved in setting cell shape, adhesion, and motility. Among direct  ladybird  targets, we identified  bric-a-brac 2  gene as a new component of identity code and  inflated  encoding αPS2-integrin playing a pivotal role in cell–cell interactions. Unexpectedly,  ladybird  also contributes to the regulation of terminal differentiation genes encoding structural muscle proteins or contributing to muscle contractility. Thus, the identity gene-governed diversification of cell types is a multistep process involving the transcriptional control of genes determining both morphological and functional properties of cells.

Genome-wide view of cell fate specification: ladybird acts at multiple levels during diversification of muscle and heart precursors