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Antagonistic regulation of p57kip2 by Hes/Hey downstream of Notch signaling and muscle regulatory factors regulates skeletal muscle growth arrest.
Development. 2014 Jul; 141(14):2780-90.D

Abstract

A central question in development is to define how the equilibrium between cell proliferation and differentiation is temporally and spatially regulated during tissue formation. Here, we address how interactions between cyclin-dependent kinase inhibitors essential for myogenic growth arrest (p21(cip1) and p57(kip2)), the Notch pathway and myogenic regulatory factors (MRFs) orchestrate the proliferation, specification and differentiation of muscle progenitor cells. We first show that cell cycle exit and myogenic differentiation can be uncoupled. In addition, we establish that skeletal muscle progenitor cells require Notch signaling to maintain their cycling status. Using several mouse models combined with ex vivo studies, we demonstrate that Notch signaling is required to repress p21(cip1) and p57(kip2) expression in muscle progenitor cells. Finally, we identify a muscle-specific regulatory element of p57(kip2) directly activated by MRFs in myoblasts but repressed by the Notch targets Hes1/Hey1 in progenitor cells. We propose a molecular mechanism whereby information provided by Hes/Hey downstream of Notch as well as MRF activities are integrated at the level of the p57(kip2) enhancer to regulate the decision between progenitor cell maintenance and muscle differentiation.

Authors+Show Affiliations

UPMC Paris 06, U 974, Paris, F-75013, France INSERM, Avenir Team, Pitié-Salpétrière, Paris, F-75013, France Institut de Myologie, Paris, F-75013, France.UPMC Paris 06, U 974, Paris, F-75013, France INSERM, Avenir Team, Pitié-Salpétrière, Paris, F-75013, France Institut de Myologie, Paris, F-75013, France.UPMC Paris 06, U 974, Paris, F-75013, France INSERM, Avenir Team, Pitié-Salpétrière, Paris, F-75013, France Institut de Myologie, Paris, F-75013, France.Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.UPMC Paris 06, U 974, Paris, F-75013, France INSERM, Avenir Team, Pitié-Salpétrière, Paris, F-75013, France Institut de Myologie, Paris, F-75013, France.UPMC Paris 06, U 974, Paris, F-75013, France INSERM, Avenir Team, Pitié-Salpétrière, Paris, F-75013, France Institut de Myologie, Paris, F-75013, France.UPMC Paris 06, U 974, Paris, F-75013, France INSERM, Avenir Team, Pitié-Salpétrière, Paris, F-75013, France Institut de Myologie, Paris, F-75013, France.Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.UPMC Paris 06, U 974, Paris, F-75013, France INSERM, Avenir Team, Pitié-Salpétrière, Paris, F-75013, France Institut de Myologie, Paris, F-75013, France frelaix@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25005473

Citation

Zalc, Antoine, et al. "Antagonistic Regulation of P57kip2 By Hes/Hey Downstream of Notch Signaling and Muscle Regulatory Factors Regulates Skeletal Muscle Growth Arrest." Development (Cambridge, England), vol. 141, no. 14, 2014, pp. 2780-90.
Zalc A, Hayashi S, Auradé F, et al. Antagonistic regulation of p57kip2 by Hes/Hey downstream of Notch signaling and muscle regulatory factors regulates skeletal muscle growth arrest. Development. 2014;141(14):2780-90.
Zalc, A., Hayashi, S., Auradé, F., Bröhl, D., Chang, T., Mademtzoglou, D., Mourikis, P., Yao, Z., Cao, Y., Birchmeier, C., & Relaix, F. (2014). Antagonistic regulation of p57kip2 by Hes/Hey downstream of Notch signaling and muscle regulatory factors regulates skeletal muscle growth arrest. Development (Cambridge, England), 141(14), 2780-90. https://doi.org/10.1242/dev.110155
Zalc A, et al. Antagonistic Regulation of P57kip2 By Hes/Hey Downstream of Notch Signaling and Muscle Regulatory Factors Regulates Skeletal Muscle Growth Arrest. Development. 2014;141(14):2780-90. PubMed PMID: 25005473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antagonistic regulation of p57kip2 by Hes/Hey downstream of Notch signaling and muscle regulatory factors regulates skeletal muscle growth arrest. AU - Zalc,Antoine, AU - Hayashi,Shinichiro, AU - Auradé,Frédéric, AU - Bröhl,Dominique, AU - Chang,Ted, AU - Mademtzoglou,Despoina, AU - Mourikis,Philippos, AU - Yao,Zizhen, AU - Cao,Yi, AU - Birchmeier,Carmen, AU - Relaix,Frédéric, PY - 2014/7/10/entrez PY - 2014/7/10/pubmed PY - 2014/9/6/medline KW - Cdkn1 KW - Cell cycle regulation KW - MRF KW - Myogenesis KW - Notch signaling KW - p57kip2 SP - 2780 EP - 90 JF - Development (Cambridge, England) JO - Development VL - 141 IS - 14 N2 - A central question in development is to define how the equilibrium between cell proliferation and differentiation is temporally and spatially regulated during tissue formation. Here, we address how interactions between cyclin-dependent kinase inhibitors essential for myogenic growth arrest (p21(cip1) and p57(kip2)), the Notch pathway and myogenic regulatory factors (MRFs) orchestrate the proliferation, specification and differentiation of muscle progenitor cells. We first show that cell cycle exit and myogenic differentiation can be uncoupled. In addition, we establish that skeletal muscle progenitor cells require Notch signaling to maintain their cycling status. Using several mouse models combined with ex vivo studies, we demonstrate that Notch signaling is required to repress p21(cip1) and p57(kip2) expression in muscle progenitor cells. Finally, we identify a muscle-specific regulatory element of p57(kip2) directly activated by MRFs in myoblasts but repressed by the Notch targets Hes1/Hey1 in progenitor cells. We propose a molecular mechanism whereby information provided by Hes/Hey downstream of Notch as well as MRF activities are integrated at the level of the p57(kip2) enhancer to regulate the decision between progenitor cell maintenance and muscle differentiation. SN - 1477-9129 UR - https://www.unboundmedicine.com/medline/citation/25005473/Antagonistic_regulation_of_p57kip2_by_Hes/Hey_downstream_of_Notch_signaling_and_muscle_regulatory_factors_regulates_skeletal_muscle_growth_arrest_ L2 - http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=25005473 DB - PRIME DP - Unbound Medicine ER -