Transcriptional control of craniofacial myogenesis

Abstract

The specification of the skeletal muscle lineage in branchiomeric development is dependent on the activity of Myf5 and MyoD, two members of the myogenic regulatory factor family. The transcriptional regulation of Myf5 is controlled by a multitude of enhancers acting at different times and anatomical locations while only two enhancers have been implicated in the regulation of MyoD. We have recently shown that the correct levels of expression of Myf5 and MyoD are the result of the activation by Musculin (Msc) and Tcf21 through binding to specific enhancers and that in the absence of Msc the timing of activation of Myf5 and MyoD is not affected but the expression levels are significantly reduced. We have now undertaken a comprehensive analysis of the different Myf5 branchial arch enhancers and we show that their function in isolation are not equivalent to their function in the context of the locus. By generating several BAC constructs carrying different deletion combinations of these enhancers we are starting to understand their functional relationship within the locus. Finally, we are studying the interactions between genes involved in branchiomeric development (Tbx1, Pitx2, Msc, Tcf21, Myf5 and MyoD) to understand the complex regulatory mechanisms behind the pattern formation during development.