Résumé :
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The diversity of human muscles is necessary to achieve proper coordinated movements. Each muscle displays a distinctive set of properties: size, shape, orientation, attachment sites to the skeleton and specific innervation. The fundamental question then arises of the molecular and cellular mechanisms controlling muscle identity. Our laboratory uses the fruit fly, Drosophila melanogaster, as a model organism to study this question. The Drosophila embryonic somatic musculature shows a highly stereotyped pattern of around 30 different muscles per hemisegment, each muscle being made of a single multinucleated fibre. Two essential steps of muscle formation can be distinguished: 1) the "specification" step whereby muscle identity is specified by the expression in each muscle precursor of a specific combination of identity transcription factors (iTF) and 2) the "realisation" step where the gene expression programme downstream of iTFs and the generic muscle differentiation program are integrated. Our laboratory has been using for several years the Dorsal Acute 3 muscle (DA3) as paradigm to study the control of muscle identity. The DA3 muscle is the only muscle which expresses the transcription factor Collier (Col), the ortholog of mammalian Early-B Cell Factor. In colmutant embryos, theDA3 muscle is transformed into a more dorsal muscle and acquires a DA2-like muscle identity, indicating that Col is required to specify the DA3 muscle identity.We are currently performing genomescale screens to identify new components and regulators of the iTF code and new genes downstream of this code:- A genetic screen for DA3 muscle defects, based on Col immunostaining. We are using a collection of small overlapping deficiencies covering chromosomes 2 and 3 (80% of the genome) and select chromosomal regions/genes required for specification and differentiation of the DA3 muscle. Identification of a new iTF will be presented.- A gene expression profiling of different muscles (DA3, DA2) expressing different combinations of iTF in order to "identify realisator genes" acting downstream of iTF. We are currently adapting a TU-tagging strategy followed by RNAseq. - A Chip-SEQ analysis of Col direct targets Since both some iTFs and muscle differentiation genes are conserved between vertebrate and invertebrates, studies in Drosophila are expected to lead to new discoveries relevant to the understanding and treatment of human muscular pathologies.
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