Dr Frédéric Relaix and his team (UMRS 787 - Myology Group) have just published an article in the journal Developmental Cell*. Their work highlights the interactions between two tissues during embryonic growth, muscles and nerves.

What was the idea behind this study?
The initial question was to know how functional adult tissues formed and at what stage the interactions essential for their correct functioning are established with surrounding tissues.
From there, we conducted a series of experiments on cultured cells and in mouse models that have shown that interactions between nerve and muscular tissues are taking place very early during development, resulting in coordinated growth. Even though it is known that during growth the muscle sends signals to the nerve, in our study we have demonstrated a very early control signal originating in the nerve and directed towards the muscle.

Can you clarify the mechanism of this signal?
Neuregulin1 synthesized by neural crest cells (NCC) binds to ErbB3 receptors of muscle cells and modulates downstream the cascade of events involved in myogenesis.
Experimentally, we started with observations on mice with specific defects in the peripheral nervous system and neural crest cells (NCC). They also had weakened skeletal muscles and showed a depletion of skeletal muscle progenitor cells due to premature entry into differentiation. Other experiments on cultured cells and in  neuregulin deficient mice, have allowed us to confirm the results.

What are the next steps?
We now know that for an adult tissue to work, it is necessary that the interactions between its components be established very early. But does this interaction continue in adults under normal circumstances? Does it continue during muscle regeneration in cases of trauma, strenuous exercise (sport) or disease? Does the elimination of neuregulin in adults affect muscle regeneration? We will try to answer these questions soon, but we have already begun to investigate whether patients with rare or common neuromuscular diseases are carriers of this type of defect.

*Neural Crest Cell Lineage Restricts Skeletal Muscle Progenitor Cell Differentiation through Neuregulin1-ErbB3 Signaling. Ho AT, Hayashi S, Brohl D, Aurade F, Rattenbach R, Relaix F.
Dev Cell, 2011 Aug 16;21(2):273-87.

 

 September 2011
Interview by Anne Berthomier, translation by Racquel N. Cooper