Skeletal muscle influence on neural development

A fundamental issue in neuronal development is to understand what factors influence the differentiation of a neuron so that it expresses its characteristic traits. These factors can be genetic (intrinsic) or non-genetic (extrinsic). I will employ knock-out mice and investigate the dependence of nervous system development on extrinsic cues provided by the skeletal muscle. I will study in vivo nervous system development in the complete absence of skeletal myogenesis (i.e., using Myf5-/-:MyoD-/- or amyogenic embryos) or in the presence of inadequately differentiated myogenic precursor cells (i.e., using MyoD-/-, Myf5-/- and Myf5-/-:MyoD-/- embryos). I expect to understand underlying mechanisms by which neurotrophic factors from the skeletal muscle influence neuronal development. I anticipate finding which neurotrophic factor is responsible for survival and maintenance of different motor and sensory neurons. In conclusion, I believe that my findings will increase our understanding of human disorders characterized with motor control disturbances and be relevant to a number of human muscular diseases.