Redefining the genetic hierarchies controlling skeletal myogenesis: Pax- 3 and Myf-5 act upstream of MyoD

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Abstract

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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Tajbakhsh, S., Rocancourt, D., Cossu, G., & Buckingham, M. (1997). Redefining the genetic hierarchies controlling skeletal myogenesis: Pax- 3 and Myf-5 act upstream of MyoD. Cell, 89(1), 127–138. https://doi.org/10.1016/S0092-8674(00)80189-0

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