title: Variations in the efficiency of lineage marking and ablation confound distinctions between myogenic cell populations.
abstract: The myogenic regulatory genes Myf5, Mrf4, Myod, and Myogenin likely arose by gene duplications during evolution, presumably to address the more demanding requirements of the vertebrate body plan. Two cell lineages were proposed to be regulated independently by Myf5 and Myod to safeguard against tissue failure. Here we report severe muscle loss following ablation of Myf5-expressing cells. Using both lineage-specific and ubiquitous reporter alleles, we show that the remaining muscles in Myf5(Cre)-DTA embryos arise mainly from Myf5(+) escaper cells. Elimination of Myf5(Cre)-DTA cells on a Myod null background did not result in the total absence of skeletal muscles, as would be expected if a Myod(+)/Myf5-independent cell population played a major role in this scenario. Therefore, these observations are incompatible with a previously proposed functional two-lineage model. These findings will have an impact on the interpretation of phenotypes obtained using similar strategies in other tissues.
authors.affiliation: Stem Cells and Development, Department of Developmental & Stem Cell Biology, URA CNRS 2578, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
authors.forename: Glenda
authors.initials: G
authors.lastname: Comai
authors.affiliation: Stem Cells and Development, Department of Developmental & Stem Cell Biology, URA CNRS 2578, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Sambasivan
authors.affiliation: Stem Cells and Development, Department of Developmental & Stem Cell Biology, URA CNRS 2578, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
authors.forename: Swetha
authors.initials: S
authors.lastname: Gopalakrishnan
authors.affiliation: Stem Cells and Development, Department of Developmental & Stem Cell Biology, URA CNRS 2578, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France. Electronic address: shahragim.tajbakhsh@pasteur.fr.
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; C063403:myogenic factor 6