Redefining the Genetic Hierarchies Controlling Skeletal Myogenesis: Pax-3 and Myf-5 Act Upstream of MyoD

Department of Molecular Biology, Centre National de la Recherche Scientifique, Unité de Recherche Associe 1947, Pasteur Institute, Paris, France.
Cell (Impact Factor: 32.24). 05/1997; 89(1):127-38. DOI: 10.1016/S0092-8674(00)80189-0
Source: PubMed


We analyzed Pax-3 (splotch), Myf-5 (targeted with nlacZ), and splotch/Myf-5 homozygous mutant mice to investigate the roles that these genes play in programming skeletal myogenesis. In splotch and Myf-5 homozygous embryos, myogenic progenitor cell perturbations and early muscle defects are distinct. Remarkably, splotch/Myf-5 double homozygotes have a dramatic phenotype not seen in the individual mutants: body muscles are absent. MyoD does not rescue this double mutant phenotype since activation of this gene proves to be dependent on either Pax-3 or Myf-5. Therefore, Pax-3 and Myf-5 define two distinct myogenic pathways, and MyoD acts genetically downstream of these genes for myogenesis in the body. This genetic hierarchy does not appear to operate for head muscle formation.

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    • "The key role of Pax genes in myogenesis is also supported by the fact that these transcription factors direct cells into the myogenic program, acting as upstream regulators of MRFs. It has been shown that Pax3 directly activates expression of Myf-5 in somites and limbs (Bajard et al. 2006; Himeda et al. 2013; Sato et al. 2010; Tajbakhsh et al. 1997) and promotes expression of MyoD via Pitx2 (L'Honore et al. 2010). "
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    • "axial skeletal muscles include the deep muscles of the back . Similar to hypaxial muscle development , epaxial muscles arise from the dorsomedial dermomyotome of the segmented paraxial mesoderm ( Figure 1 ; Christ and Ordahl , 1995 ; Burke and Nowicki , 2003 ) . While the development of epaxial muscle is well studied ( Munsterberg et al . , 1995 ; Tajbakhsh et al . , 1997 ; Borycki et al . , 1999 ; Gustafsson et al . , 2002 ; McDermott et al . , 2005 ; Borello et al . , 2006 ; L ' Honore et al . , 2010 ; Sato et al . , 2010 ) , the biological properties of adult epaxial satellite cells remain largely unknown . Mouse models expressing nLacZ under the control of the Pax3 promoter showed coexpression o"
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