Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD.
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.
Tajbakhsh
S
S
Department of Molecular Biology, Centre National de la Recherche Scientifique, Unité de Recherche Associe 1947, Pasteur Institute, Paris, France.
Rocancourt
D
D
Cossu
G
G
Buckingham
M
M
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006720:Homozygote; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D009154:Mutation / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics*; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000502:physiology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C068686:Pax3 protein, mouse