Muscle contraction is required to maintain the pool of muscle progenitors via YAP and NOTCH during fetal myogenesis
Abstract
The importance of mechanical activity in the regulation of muscle progenitors during chick development has not been investigated. We show that immobilization decreases NOTCH activity and mimics a NOTCH loss-of-function phenotype, a reduction in the number of muscle progenitors and increased differentiation. Ligand-induced NOTCH activation prevents the reduction of muscle progenitors and the increase of differentiation upon immobilization. Inhibition of NOTCH ligand activity in muscle fibers suffices to reduce the progenitor pool. Furthermore, immobilization reduces the activity of the transcriptional co-activator YAP and the expression of the NOTCH ligand JAG2 in muscle fibers. YAP forced activity in muscle fibers prevents the decrease of JAG2 expression and the number of PAX7+ cells in immobilization conditions. Our results identify a novel mechanism acting downstream of muscle contraction, where YAP activates JAG2 expression in muscle fibers, which in turn regulates the pool of fetal muscle progenitors via NOTCH in a non cell-autonomous manner.
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Funding
Agence Nationale de la Recherche (ANR-12-BSV1-0038)
- Delphine Duprez
AFM-Téléthon (AFM N{degree sign}16752/16826)
- Delphine Duprez
Fondation pour la Recherche Médicale (DEQ20140329500)
- Delphine Duprez
Centre National de la Recherche Scientifique
- Delphine Duprez
Institut National de la Santé et de la Recherche Médicale
- Delphine Duprez
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Esteves de Lima et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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