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Altered myogenesis in Six1-deficient mice
Christine Laclef1, Ghislaine Hamard, Josiane Demignon
1Département Génétique, Développement et Pathologie Moléculaire, Institut Cochin - INSERM 567, CNRS UMR 8104, Université Paris V, 24 Rue du Faubourg Saint Jacques, 75014 Paris, France.
Development (Cambridge, England)
|April 2, 2003
Summary
The Six1 gene is crucial for vertebrate muscle development. Its absence leads to severe muscle defects and embryonic death, highlighting its specific role in hypaxial muscle differentiation.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Six homeoproteins are expressed during vertebrate embryogenesis, suggesting roles in differentiation.
- The specific function of the Six1 gene in myogenesis (muscle development) was not fully understood.
Purpose of the Study:
- To investigate the function of the Six1 gene during myogenesis.
- To determine the consequences of Six1 deficiency in mice.
Main Methods:
- Construction of Six1-deficient mice by replacing the first exon with the lacZ gene.
- Analysis of embryonic development, focusing on muscle formation and gene expression in Six1(-/-) embryos.
Main Results:
- Six1-deficient mice exhibit severe rib malformations and die at birth.
- Extensive muscle hypoplasia was observed in most body muscles, particularly hypaxial muscles.
- Primary myogenesis was impaired, with reduced and disorganized primary myofibers.
- While early myogenic gene expression in somites was normal, MyoD and myogenin activation was delayed in limb buds by E11.5.
- Cell migration and apoptosis of myoblasts were not responsible for the observed defects.
Conclusions:
- Six1 plays a critical and specific role in hypaxial muscle differentiation.
- The function of Six1 in myogenesis is distinct from other known hypaxial determinants like Pax3, cMet, Lbx1, or Mox2.