CHARACTERIZATION OF PATHWAYS REGULATING CELL CYCLE AND MUSCLE-SPECIFIC TRANSCRIPTION DURING MYOGENIC DIFFERENTIATION: THERAPEUTICAL IMPLICATIONS FOR MUSCLE REGENERATION

The proposed project is aimed at investigating the molecular basis that regulate the expression of genes implicated in skeletal muscle cell differentiation. The acquisition of these informations is essential to design therapeutical approaches to stimulate muscle regeneration in genetic and acquired skeletal muscle diseases. Organ regeneration represents an immediate therapeutical tool in these diseases, but is hampered by two main problems: 1) the inability of skeletal myofibers to proliferate and generate new muscle cells; 2) the low efficiency to repopulate the damaged muscle by a population of resting myogenic precursors that normally surround muscle fibers. This research is aimed at the identification of those biochemical mechanisms that can be used to manipulate critical cellular function and thereby enhance the efficiency of muscle regeneration. The identification of reversible modifications in proteins devoted to the control the myogenic program is a critical acquisition in order to decipher the biochemical code regulating muscle growth and differentiation. Only the deep knowledge of this code will allow a pharmacological manipulation of muscle regeneration. The present project is aimed at a) identifying those genes that must be repressed to inhibit regeneration from mature skeletal muscle fibers and b) to uncover the importance of a reversible modification (acetylation) of proteins involved in the control of the myogenic program. This modification may be a potential pharmacological target in therapies for neuromuscular diseases