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Article Dans Une Revue Developmental Biology Année : 2011

Genesis of muscle fiber-type diversity during mouse embryogenesis relies on Six1 and Six4 gene expression

Josiane Demignon
  • Fonction : Auteur
Iori Sakakibara
  • Fonction : Auteur
Julien Pujol
  • Fonction : Auteur
Maryline Favier
  • Fonction : Auteur
Laure Strochlic
  • Fonction : Auteur
Fabien Le Grand
  • Fonction : Auteur
Nicolas Sgarioto
  • Fonction : Auteur
Anthony Guernec
Alain Schmitt
  • Fonction : Auteur
Nicolas Cagnard
  • Fonction : Auteur
Ruijin Huang
  • Fonction : Auteur
Claire Legay
  • Fonction : Auteur
Pascal Maire
  • Fonction : Auteur

Résumé

Adult skeletal muscles in vertebrates are composed of different types of myofibers endowed with distinct metabolic and contraction speed properties. Genesis of this fiber-type heterogeneity during development remains poorly known, at least in mammals. Six1 and Six4 homeoproteins of the Six/sine oculis family are expressed throughout muscle development in mice, and Six1 protein is enriched in the nuclei of adult fast-twitch myofibers. Furthermore, Six1/Six4 proteins are known to control the early activation of fast-type muscle genes in myocytes present in the mouse somitic myotome. Using double Six1:Six4 mutants (SixdKO) to dissect in vivo the genesis of muscle fiber-type heterogeneity, we analyzed here the phenotype of the dorsal/epaxial muscles remaining in SixdKO. We show by electron microscopy analysis that the absence of these homeoproteins precludes normal sarcomeric organization of the myofiber leading to a dystrophic aspect, and by immunohistochemistry experiments a deficiency in synaptogenesis. Affymetrix transcriptome analysis of the muscles remaining in E18.5 SixdKO identifies a major role for these homeoproteins in the control of genes that are specifically activated in the adult fast/glycolytic myofibers, particularly those controlling Ca(2+) homeostasis. Absence of Six1 and Six4 leads to the development of dorsal myofibers lacking expression of fast-type muscle genes, and mainly expressing a slow-type muscle program. The absence of restriction of the slow-type program during the fetal period in SixdKO back muscles is associated with a decreased HDAC4 protein level, and subcellular relocalization of the transcription repressor Sox6. Six genes thus behave as essential global regulators of muscle gene expression, as well as a central switch to drive the skeletal muscle fast phenotype during fetal development.

Dates et versions

hal-04532076 , version 1 (04-04-2024)

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Citer

Anne-Françoise Richard, Josiane Demignon, Iori Sakakibara, Julien Pujol, Maryline Favier, et al.. Genesis of muscle fiber-type diversity during mouse embryogenesis relies on Six1 and Six4 gene expression. Developmental Biology, 2011, 359 (2), pp.303-320. ⟨10.1016/j.ydbio.2011.08.010⟩. ⟨hal-04532076⟩

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