Résumé :
|
Although much is known about skeletal muscle biology, we have only recently begun to appreciate how stem and progenitor cells establish this tissue through the action of key regulatory genes. In the mouse embryo, the dermomyotome (DM) harbors stem cells for multiple cell lignages including muscle. The DM is the epithelium of the somite which assures a continuous source of muscle progenitor cells (MPCs) from the stem cells expressing Pax3 and Pax7. Muscle progenitors generate myoblasts which differentiate to form the first skeletal mass in the somite, the myotome. To study self-renewal and differentiation of MPCs, we are investigating self-renewal via asymmetric divisions. The cell fate determinant Numb has been implicated in asymmetric division and involved in binary cell fate choices via Notch inhibition in Drosophila. However, the mechanisms and the role of Numb involved in generating cell diversity in vertebrates remains unclear. To further assess the role of Numb in driving cell fate in the mouse dermomyotome and in establishing the myotome, several transgenics were made to study the effects of Numb-GFP over-expression in the somite using the epaxial enhancer of Myf5. First we show that these transgenics do drive NumbGFP over-expression in most of the stem cells of the dorsal somite. Unexpectedly this strategy revealed that the overexpression of Numb-GFP in the dorsal dermomyotome only very mildly affects cell fate decisions and does not seem to have an effect on Notch signalling in this context. We do not observe an overt increase of muscle differentiation in the dorsal somite. Thus, we believe that Numb and Notch act in particular cell states in lineage progression. Interestingly, this strategy revealed a novel role for Numb in somite patterning, in the epithelial organisation of the dermomyotome, as well as in myofiber organisation in the underlying myotome.
|