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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    • "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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    ABSTRACT: Citation: Randolph ME and Pavlath GK (2015) A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups. The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease.
    Frontiers in Aging Neuroscience 10/2015; 7. DOI:10.3389/fnagi.2015.00190 · 4.00 Impact Factor
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    • "All body muscles and part of the tongue musculature are established from founder stem cells located in transient structures called somites, and they are under the regulation of the paired/ homeobox transcription factors Pax3 and Pax7 (Kassar-Duchossoy et al., 2005; Relaix et al., 2005). In contrast, the founder stem cells of cranial muscles do not express Pax3 (Relaix et al., 2004), as they are regulated by a distinct genetic program (Sambasivan et al., 2009; Tajbakhsh et al., 1997). As chordates evolved from filter feeders to active predators, the newly elaborated head and mastication muscles developed from the cranial mesoderm, which is regulated by a distinct set of upstream genes, particularly Tbx1, Pitx2, and Islet1 (Isl1) (Diogo et al., 2015; Grifone and Kelly, 2007; Harel et al., 2009). "
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    ABSTRACT: The esophagus links the oral cavity to the stomach and facilitates the transfer of bolus. Using genetic tracing and mouse mutants, we demonstrate that esophagus striated muscles (ESMs) are not derived from somites but are of cranial origin. Tbx1 and Isl1 act as key regulators of ESMs, which we now identify as a third derivative of cardiopharyngeal mesoderm that contributes to second heart field derivatives and head muscles. Isl1-derived ESM progenitors colonize the mouse esophagus in an anterior-posterior direction but are absent in the developing chick esophagus, thus providing evolutionary insight into the lack of ESMs in avians. Strikingly, different from other myogenic regions, in which embryonic myogenesis establishes a scaffold for fetal fiber formation, ESMs are established directly by fetal myofibers. We propose that ESM progenitors use smooth muscle as a scaffold, thereby bypassing the embryonic program. These findings have important implications in understanding esophageal dysfunctions, including dysphagia, and congenital disorders, such as DiGeorge syndrome.
    Developmental Cell 09/2015; 34(6). DOI:10.1016/j.devcel.2015.07.003 · 9.71 Impact Factor
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    • "In contrast, mice lacking both Pax3;Myf5 (and Mrf4) had no trunk muscles, yet retain normal head muscles (Tajbakhsh et al. 1997). Thus, in the absence of Myf5, Pax3 is necessary for the expression of MyoD in the trunk, but not in the head, a finding consistent with the fact that Pax3 is not expressed in head muscle progenitors (Hacker and Guthrie 1998; Harel et al. 2009; Tajbakhsh et al. 1997) (Fig. 1). A recent study in mice that addressed the genetic programs promoting myogenesis in the head revealed distinct requirements for Myf5 and Mrf4 in extraocular muscles (EOM) and in pharyngeal muscles (Sambasivan et al. 2009). "

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