Neuromuscular junction morphology, fiber-type proportions, and satellite-cell proliferation rates are altered in MyoD(-/-) mice.
Gene compensation by members of the myogenic regulatory factor (MRF) family has been proposed to explain the apparent normal adult phenotype of MyoD(-/-) mice. Nerve and field stimulation were used to investigate contraction properties of muscle from MyoD(-/-) mice, and molecular approaches were used to investigate satellite-cell behavior. We demonstrate that MyoD deletion results in major alterations in the organization of the neuromuscular junction, which have a dramatic influence on the physiological contractile properties of skeletal muscle. Second, we show that the lineage progression of satellite cells (especially initial proliferation) in the absence of MyoD is abnormal and linked to perturbations in the nuclear localization of beta-catenin, a key readout of canonical Wnt signaling. These results show that MyoD has unique functions in both developing and adult skeletal muscle that are not carried out by other members of the MRF family.
Macharia
Raymond
R
Department of Veterinary Basic Sciences, Royal Veterinary College, London, NW1 0TU, UK.
Otto
Anthony
A
Valasek
Petr
P
Patel
Ketan
K
D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D004558:Electric Stimulation; D006019:Glycolysis / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000145:classification / Q000648:ultrastructure*; D017570:MyoD Protein / Q000235:genetics*; D009469:Neuromuscular Junction / Q000648:ultrastructure*; D019913:Nuclear Localization Signals / Q000502:physiology; D010084:Oxidation-Reduction; D032496:Satellite Cells, Skeletal Muscle / Q000648:ultrastructure*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D019913:Nuclear Localization Signals; D051176:beta Catenin; D013385:Succinate Dehydrogenase