June 15, 2005
The embryonic origin of muscle stem cells
Researchers from the CNRS and the Institut Pasteur, members of the European Network of Excellence MYORES report on the embryonic origins of muscle stem cells. These results, published in two Nature papers on June 16th, 2005, lead to a better understanding of the muscle development.
Muscle stem cells exist in the embryo and in the adult In the embryo and the fetus proliferation of these cells leads to muscle growth. In the adult, muscle stem cells called “satellite cells” are located along the muscle fibers in a quiescent state. The activation and proliferation of these cells on intense physical exercice leads to an increase of muscle mass in the adult. These cells also play a critical role in muscle repair. In elderly people these cells have a reduced ability to multiply, which leads to a reduction in their muscle mass.
Using the chicken as a model, Christophe Marcelle’s laboratory, from the Institute of Developmental Biology in Marseille (CNRS / Univerty of Aix – Marseille2) identified the origins of the muscle stem cells in the embryo and the fetus. They come from embryonic structures called somites.
Furthermore, they has shown that the muscle stem cells of the embryo give birth to the satellite cells of the adult. Therefore all muscle stem cells, whether embryonic, foetal or adult, have the same embryonic origin, deriving from the somites.
At the same time, Margaret Buckingham’s laboratory (1) (Institut Pasteur / CNRS), using the mouse as a model, has shown that the presence of these muscle stem cells depends on the function of two genes called Pax3 and Pax7. When both these genes are inactived, there are no muscle stem cells, and muscle growth is arrested.
These results will enable scientists to better understand the biology of these cells and how the muscle masses of the embryo and the adult increase. It should be possible to further characterise the mechanisms through which these cells use their muscle potential, and to examine whether pharmaceutical components can increase their ability to generate new muscles.
These studies also open new horizons for cellular therapies of muscle diseases. Satellite cells enable the replacement of damaged muscle fibers, but they cannot compensate for major pathological damage. In the future, the embryo’s muscle stem cells may prove to be of therapeutic value, when genetically modified or not, and reimplanted in the adult organism. This kind of therapy has already been used on humans for some neurodegenerative diseases such as Huntington and Parkinson diseases, already with promising results.
In Europe, over 300 000 people are affected with muscle dystrophies, and most of the older population suffers from muscular degeneration linked with ageing. These affections, leading to a reduced mobility and the loss of independence, have severe consequences on everyday life as well as creating economic problems.
These researches have been financed jointly by the integrated project EuroStemCell (European research consortium on stem cells) and the AFM (French Association against Myopathies). The staff is a member of the European Network of Excellence MYORES.
The European Network of Excellence MYORES
MYORES, of which the two laboratories are members, includes 23 institutions in 7 different countries. It is the first network of this size to study muscle development. Coordinated by Inserm and managed by Inserm-Transfert, it is one of the priorities of the 6th Framework Program for Research and Technological Development (FP6) of the European Commission. It was granted a 12 million Euro budget over 5 years.
Research undertaken within this network clearly shows that the cellular and molecular mechanisms that are vital to human muscle growth exist not only in other vertebrates but also in invertebrates, like the fly or the worm. In these animal models, it will be possible to dissect the mechanisms of muscle formation and to understand them more easily. The acquisition of this knowledge will enable the network members to progress more rapidly in understanding the various stages of muscle formation. By carrying out tests on several hundreds of genes, they will be able to identify future therapeutic targets.
Margaret Buckingham’s laboratory is also a member of another network of excellence “Cells into Organs”, and of an integrated project “EuroStemCell” from the European Commission, which funded this project.
Jérôme Gros, Marie Manceau, Virginie Thomé, Christophe Marcelle,
Laboratoire de Genetique et de Physiologie du Developpement,Universite de la Méditerranée, Campus de Luminy, 13288 Marseille
" A Pax3/Pax7 – dependent population of skeletal muscle progenitor cells " Nature 16 juin 2005 .
Frédéric Relaix, Didier Rocancourt, Ahmed Mansourt, Margaret Buckingham
Unité de Génétique Moléculaire du Développement, Institut Pasteur/CNRS
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