Regulation of Muscle Stem Cell Fate

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• Professor Margaret Buckingham from Department of Developmental Biology, Pasteur Institute, Paris
• Thursday 14 February 2013, 14:30-15:30
• Part II Room, Department of Genetics.

If you have a question about this talk, please contact Caroline Newnham.

Pax transcription factors play important roles in the regulation of organ and tissue development (1). In the case of skeletal muscle, Pax3, together with its orthologue Pax7, when it is expressed, controls key steps in the myogenic progression of multipotent mesodermal stem cells, including cell fate choice (2), self-renewal and the entry of cells into the myogenic programme in the embryo. Once a myogenic determination gene, such as Myf5 or MyoD, is activated, cells differentiate to form muscle fibres. In the adult, satellite cells, present under the basal lamina of fibres, are the progenitor cells responsible for muscle regeneration. These cells are marked by the expression of Pax7 and, in many muscles, also Pax3. However, unlike the Pax-positive muscle progenitor cells of the embryo, most satellite cells already transcribe the myogenic determination gene, Myf5, but do not activate the myogenic programme. MicroRNA-31 regulation of Myf5mRNA, together with sequestration of this microRNA with Myf5mRNA in ribonucleoprotein particles, characterises the quiescent satellite cell. On activation, this post-transcriptional repression is released and the cell rapidly enters the myogenic programme (3). We therefore propose a model in which post-transcriptional mechanisms in the adult, hold quiescent stem cells poised to enter a tissue specific differentiation programme.

(1) Buckingham, M., & Relaix, F. (2007). The role of Pax genes in the development of tissues and organs : Pax3 and Pax7 regulate muscle progenitor cell functions. Ann. Rev. Cell Dev. Biol. 23, 645-673. (2) Lagha, M., Brunelli, S., Messina, G., Kume, T., Relaix, F., & Buckingham, M.E. (2009). Pax3/7:Foxc2 reciprocal repression in the somite modulates multipotent stem cell fates. Dev. Cell, 17, 892-899. (3) Crist, C., Montarras, D., & Buckingham, M. (2012). Muscle satellite cells are primed for myogenesis, but maintains quiescence with sequestration of Myf5 mRNA targeted by microRNA-31 in mRNP granules. Cell Stem Cell. 11, 118-126.

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