title: 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.
authors.affiliation: CNRS UMR 7622, F-75005 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|IBPS-Developmental Biology Laboratory, Paris, France.|Inserm U1156, F-75005, Paris, France.
authors.forename: Joana
authors.identifier: 0000-0002-5497-5669
authors.initials: J
authors.lastname: Esteves de Lima
authors.affiliation: CNRS UMR 7622, F-75005 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|IBPS-Developmental Biology Laboratory, Paris, France.|Inserm U1156, F-75005, Paris, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Bonnin
authors.affiliation: Developmental Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
authors.affiliation: CNRS UMR 7622, F-75005 Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|IBPS-Developmental Biology Laboratory, Paris, France.|Inserm U1156, F-75005, Paris, France.
authors.forename: Delphine
authors.identifier: 0000-0003-0248-7417
authors.initials: D
authors.lastname: Duprez
mesh_terms: D000818:Animals; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D000072101:Jagged-2 Protein / Q000378:metabolism*; D009119:Muscle Contraction; D024510:Muscle Development; D051880:Receptors, Notch / Q000378:metabolism*; D013234:Stem Cells / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D000072101:Jagged-2 Protein; D051880:Receptors, Notch; D015534:Trans-Activators
keywords: NOTCH; YAP; chick; chicken; developmental biology; limb; mechanics; myogenesis; stem cells