The inability of the muscle to repair itself during aging or disease is not necessarily due to an irreversible loss of progenitor cells or their repair potential. Rather, it is caused by mis-activation of a recently-described signalling pathway called “Notch.” This is the conclusion drawn by the team of T.A. Rando of the University of Stanford (California), and presented at the Congress of Myology in Nantes.
In normal conditions the Notch signalling pathway plays an important role in the different phases of activation, proliferation and differentiation of primitive muscle stem cells, satellite cells and their daughter cells. The inhibition of Notch considerably affects the regenerative process of the muscle. In satellite cells, the activation of this signalling pathway in response to traumatisms (physical or other aggressions) varies with age. One of the key aspects of the impairment of the Notch signalling pathway in old tissue lies in its incapacity to regulate positively the expression of “delta,” the Notch ligand. In the absence of induction of this delta factor, the Notch signalling pathway is not activated and satellite cells cannot regenerate sufficiently to repair effectively the damaged muscle. In this context, we have been able to demonstrate that old satellite cells retain their intrinsic regenerative potential but that it was their environment which limited this potential. When Notch is directly stimulated without induction of the delta ligand, old satellite cells are as effective as young ones. Even more surprising, when the muscles of older mice are exposed for a sufficient time to an environment coming from younger mouse muscles containing the delta factor, the muscle regeneration in the older mice is identical to that in the younger, proving that the satellite cells of old mice retain a young phenotype, at both molecular and histological level. This opens therapeutic approaches in the struggle against physiological muscle aging as well as in certain neuromuscular diseases. These approaches are to be explored with precaution due to the potential risk of anarchic muscle development.
> Contribution by Thomas Rando, tuesday 10 may 17h30

The team of Krysztof Jagla (Inserm laboratory Unit 384, Clermont-Ferrand, France and coordinator of the Myores European network) has shown that the development of the leg of the drosophila (more commonly known as the fruit-fly) is intimately associated with the formation of tendons, which are elements attaching body muscles to bones. In the drosophila, the only muscles attached to tendons are called appendicular muscles.
The musculature of the leg of the drosophila has not been studied since 1950 even though it presents many interesting similarities with the muscles of vertebrates, including man.
For the first time, the relationship between tendon structures and muscle fibres has been studied in depth. Using specific markers, the researchers were able to observe the procedure of appendicular myogenesis in the drosophila and show it on a very original 3D representation of muscle fibres.
In the process of muscle formation, the function of the EGF (endothelium growth factor) receptor is crucial for the correct attachment of the tendons to muscles.
Understanding muscle-tendon interactions is a little-studied problem, yet a very important one in certain myopathies. It is known that dystrophin (a protein absent in Duchenne myopathy) is abundant in this atomic zone.