Ricerc@Sapienza

State of the Art
Skeletal muscle has an extraordinary regenerative capacity thanks to the presence of adult muscle stem cells named Satellite Cells (MuSC). Despite the ability of the MuSC to regenerate the muscle after damage, skeletal muscle regeneration is functionally successful only when the newly formed myo¿bres become innervated through the establishment of new Neuro-Muscular Junctions (NMJs). The mechanisms that regulate the growth or extension of neurites toward regenerating fibers and the timing of functional synaptic reestablishment on a regenerating ¿ber remain unclear and unexplored. Moreover, loss of NMJ in the intact muscle tissue leads to muscle atrophy consistent with the vital role of NMJ in muscle maintenance and homeostasis.

General interest of the project
Recently we demonstrate that not only muscle fibers are sensitive to muscle innervation. Indeed, alteration of the neuromuscular integrity - due to either traumatic or genetic disease - activate a specific gene expression program in muscle resident cell populations. In this proposal we aim to explore the cellular and molecular network that coordinate NMJ integrity.

Objectives and Methodology
We will, for the first time, dissect the role of glial cells in skeletal muscle regeneration and their cross talk with muscle resident cell populations. We will use a lineage tracing mouse models to better analyze the involvement of this population in muscle maintenance and regeneration. Finally, we will couple in-vivo study with next-generation sequencing approach and in-vitro culture system to tackle this unexplored faced of muscle biology.

Conclusions
This study will pave the way to the discovery of new cellular and molecular targets in neuromuscular disease or in pathologies characterized by nerve degeneration and muscle fibers regeneration.