CONTROL OF AXIAL MUSCLE DEVELOPMENT

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Determination, differentiation, and patterned morphogenesis are central processes during development, but the mechanisms controlling them have yet to be satisfactorily identified. These processes are accessible to analysis in a simple vertebrate system, the development of axial muscle from the epithelial dermatome in the chicken embryo. Pilot studies suggest that the dermatome generates two cell phenotypes under a tight spatial control. Furthermore, this generation pattern can be altered experimentally. A simple surgery causes the dermacyte-forming population to form myocytes instead. Moreover, the dermatome gives rise to axial muscles that manifest different fates at limb and thoracic levels. For instance, preliminary results show that programmed death of dermatome prevents development of lateral axial muscles at limb levels and suggest that this death is induced by an interaction with limb tissue. Proposed studies focus on the spatial control of cell generation in this system and the interactions controlling cell generation patterns and muscle fate. Studies in five aims will 1) finely map the fate of dermatome cells and characterize the development of muscles derived from dermatome, 2) assess the pluripotency of spatially defined dermatomal populations, 3) define interactions that control the patterned generation of myocytes and dermacytes, 4) define interactions that control the segment-specific fates of axial muscles and 5) assess the relevance of putative regulatory genes by defining expression patterns and using experimental manipulations. The approaches combine anatomical methods, fate-mapping strategies and embryonic surgeries. This work will help elucidate mechanisms that control the patterned generation of specific cell types and the morphogenesis of muscles, processes that are fundamental to normal human development.