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Skeletal myogenesis is initiated by the activation of the Mrf4/Myf5 locus which is expressed in multiple regions of the embryo in response to signals which are interpreted by an exceptionally complex array of regulatory elements. This triggers a cascade of transcription factors and downstream structural genes, ultimately resulting in the generation of one of the fundamental histotypes. Our work will provide specific answers to a number of outstanding questions in developmental biology, such an in-depth study of the molecular biology of craniofacial muscle development which has been little characterised in mammals, transcriptional regulation, including the full characterization of particular elements involved in crucial regulatory aspects of the locus and the analysis of a novel mechanism for regulating complex loci. Finally, understanding the upstream signalling systems will open the way to studies of molecular evolution and of regeneration and repair in the adult.
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