Julie Melendez

Skeletal muscles are formed of multinucleated fibers. Muscle fusion is a crucial process that starts during embryogenesis and continues throughout lifetime during growth and repair. Fusion is tightly regulated in time and space. In fact, over-fusion leads to aberrant muscle masses whereas defect in fusion induces abnormal formation and/or repair of the muscles. The fusion process has been studied for years and many genes are known to be involved in this process.

Most of them are required for fusion: during cell-cell recognition, adhesion, actin rearrangement or for transcriptional regulation. This field of research is still in expansion, recently new crucial pro-fusion genes have been identified, such as Myomaker and Myomerger. Even if the cellular events of fusion are well understood, the cellular and molecular mechanisms regulating fusion are more obscure. The goal of my work was to understand the dynamics and molecular mechanisms underlying this process during early muscle formation, particularly to identify inhibitors of fusion.

A C2C12 esiRNA screen performed in our lab identified a number of genes involved in fusion regulation. Among them, the TGF-beta superfamily was identified as inhibitor of fusion without impacting on muscle differentiation. During my thesis I used in situ hybridization and in ovo electroporation in the chicken embryo to decipher the role of TGF-beta signaling in vivo during myogenesis. I show that TGF-beta regulates the pace of fusion by acting as a molecular brake of muscle fusion in vivo during the first step of myogenesis.