Overlapping functions of SIX homeoproteins during embryonic myogenesis

PLoS Genet. 2023 Jun 2;19(6):e1010781. doi: 10.1371/journal.pgen.1010781. eCollection 2023 Jun.


Four SIX homeoproteins display a combinatorial expression throughout embryonic developmental myogenesis and they modulate the expression of the myogenic regulatory factors. Here, we provide a deep characterization of their role in distinct mouse developmental territories. We showed, at the hypaxial level, that the Six1:Six4 double knockout (dKO) somitic precursor cells adopt a smooth muscle fate and lose their myogenic identity. At the epaxial level, we demonstrated by the analysis of Six quadruple KO (qKO) embryos, that SIX are required for fetal myogenesis, and for the maintenance of PAX7+ progenitor cells, which differentiated prematurely and are lost by the end of fetal development in qKO embryos. Finally, we showed that Six1 and Six2 are required to establish craniofacial myogenesis by controlling the expression of Myf5. We have thus described an unknown role for SIX proteins in the control of myogenesis at different embryonic levels and refined their involvement in the genetic cascades operating at the head level and in the genesis of myogenic stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins* / metabolism
  • Mice
  • Muscle Development / genetics
  • Muscle, Skeletal / metabolism
  • Somites* / metabolism


  • Homeodomain Proteins

Grants and funding

MW is supported by the University Paris Cité (UPC), by the « Association Française contre les Myopathies » (AFM) and by the Agence Nationale pour la Recherche (ANR). RM is supported by UPC and the Fondation pour la Recherche Médicale (FRM). Financial support was provided by the AFM (AFM 17406 and AFM 16315) the Institut National de la Santé et de la Recherche Médicale (INSERM), the Centre National de la Recherche Scientifique (CNRS), and the ANR (ANR16-CE-14-0032-01 Myolinc) to PM, by the AFM 16315 to ST, and by AFM 19507 and 22946 to FR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.