Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 629K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sabourin, L. A. Articles by Rudnicki, M. A. Search for Related Content PubMed PubMed Citation Articles by Sabourin, L. A. Articles by Rudnicki, M. A. Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/1999//631 $5.00
The Journal of Cell Biology, Volume 144, Number 4, , 1999 631-643

Reduced Differentiation Potential of Primary MyoD–/– Myogenic Cells Derived from Adult Skeletal Muscle

Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada L8S 4K1

To gain insight into the regeneration deficit of MyoD–/– muscle, we investigated the growth and differentiation of cultured MyoD–/– myogenic cells. Primary MyoD–/– myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c-met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD–/– myogenic cells did not express desmin, an intermediate filament protein typically expressed in cultured myoblasts in vitro and myogenic precursor cells in vivo. Northern analysis indicated that proliferating MyoD–/– myogenic cells expressed fourfold higher levels of Myf-5 and sixfold higher levels of PEA3, an ETS-domain transcription factor expressed in newly activated satellite cells. Under conditions that normally induce differentiation, MyoD–/– cells continued to proliferate and with delayed kinetics yielded reduced numbers of predominantly mononuclear myocytes. Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally. Expression of M-cadherin mRNA was severely decreased whereas expression of IGF-1 was markedly increased in MyoD–/– myogenic cells. Mixing of lacZ-labeled MyoD–/– cells and wild-type myoblasts revealed a strict autonomy in differentiation potential. Transfection of a MyoD-expression cassette restored cytomorphology and rescued the differentiation deficit. We interpret these data to suggest that MyoD–/– myogenic cells represent an intermediate stage between a quiescent satellite cell and a myogenic precursor cell.

Key Words: MyoD • myogenic regulatory factor • satellite cell • differentiation • proliferation

Abbreviations used in this paper: BrdU, 5-bromo-2'-deoxyuridine; MHC, myosin heavy chain; MRF, myogenic regulatory factors.

M.A. Rudnicki is a research scientist of the National Cancer Institute of Canada, and a member of the Canadian Genetic Disease Network of Excellence. L.A. Sabourin is a postdoctoral fellow of the Medical Research Council of Canada, and P. Seale is supported by an National Science and Engineering Research Scholarship.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Kelly, T. J., Lerin, C., Haas, W., Gygi, S. P., Puigserver, P. (2009). GCN5-mediated Transcriptional Control of the Metabolic Coactivator PGC-1{beta} through Lysine Acetylation. J. Biol. Chem. 284: 19945-19952 [Abstract] [Full Text]  
• Kleiner, S., Nguyen-Tran, V., Bare, O., Huang, X., Spiegelman, B., Wu, Z. (2009). PPAR{delta} Agonism Activates Fatty Acid Oxidation via PGC-1{alpha} but Does Not Increase Mitochondrial Gene Expression and Function. J. Biol. Chem. 284: 18624-18633 [Abstract] [Full Text]  
• Rudnicki, M.A., Le Grand, F., McKinnell, I., Kuang, S. (2009). The Molecular Regulation of Muscle Stem Cell Function. Cold Spring Harb Symp Quant Biol 0: sqb.2008.73.064v1-sqb.2008.73.064 [Abstract]  
• Cowling, B. S., McGrath, M. J., Nguyen, M.-A., Cottle, D. L., Kee, A. J., Brown, S., Schessl, J., Zou, Y., Joya, J., Bonnemann, C. G., Hardeman, E. C., Mitchell, C. A. (2008). Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy. JCB 183: 1033-1048 [Abstract] [Full Text]  
• Sun, D., Li, H., Zolkiewska, A. (2008). The role of Delta-like 1 shedding in muscle cell self-renewal and differentiation. J. Cell Sci. 121: 3815-3823 [Abstract] [Full Text]  
• McKay, B. R., O'Reilly, C. E., Phillips, S. M., Tarnopolsky, M. A., Parise, G. (2008). Co-expression of IGF-1 family members with myogenic regulatory factors following acute damaging muscle-lengthening contractions in humans. J. Physiol. 586: 5549-5560 [Abstract] [Full Text]  
• Laurin, M., Fradet, N., Blangy, A., Hall, A., Vuori, K., Cote, J.-F. (2008). The atypical Rac activator Dock180 (Dock1) regulates myoblast fusion in vivo. Proc. Natl. Acad. Sci. USA 105: 15446-15451 [Abstract] [Full Text]  
• Bakkar, N., Wang, J., Ladner, K. J., Wang, H., Dahlman, J. M., Carathers, M., Acharyya, S., Rudnicki, M. A., Hollenbach, A. D., Guttridge, D. C. (2008). IKK/NF-{kappa}B regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis. JCB 180: 787-802 [Abstract] [Full Text]  
• Holterman, C. E., Le Grand, F., Kuang, S., Seale, P., Rudnicki, M. A. (2007). Megf10 regulates the progression of the satellite cell myogenic program. JCB 179: 911-922 [Abstract] [Full Text]  
• Watanabe, S., Kondo, S., Hayasaka, M., Hanaoka, K. (2007). Functional analysis of homeodomain-containing transcription factor Lbx1 in satellite cells of mouse skeletal muscle. J. Cell Sci. 120: 4178-4187 [Abstract] [Full Text]  
• Li, W., Wu, G., Wan, Y. (2007). The dual effects of Cdh1/APC in myogenesis. FASEB J. 21: 3606-3617 [Abstract] [Full Text]  
• Hawke, T. J., Atkinson, D. J., Kanatous, S. B., Van der Ven, P. F. M., Goetsch, S. C., Garry, D. J. (2007). Xin, an actin binding protein, is expressed within muscle satellite cells and newly regenerated skeletal muscle fibers. Am. J. Physiol. Cell Physiol. 293: C1636-C1644 [Abstract] [Full Text]  
• Deponti, D., Francois, S., Baesso, S., Sciorati, C., Innocenzi, A., Broccoli, V., Muscatelli, F., Meneveri, R., Clementi, E., Cossu, G., Brunelli, S. (2007). Necdin mediates skeletal muscle regeneration by promoting myoblast survival and differentiation. JCB 179: 305-319 [Abstract] [Full Text]  
• Asakura, A., Hirai, H., Kablar, B., Morita, S., Ishibashi, J., Piras, B. A., Christ, A. J., Verma, M., Vineretsky, K. A., Rudnicki, M. A. (2007). Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle. Proc. Natl. Acad. Sci. USA 104: 16552-16557 [Abstract] [Full Text]  
• Suelves, M., Vidal, B., Serrano, A. L., Tjwa, M., Roma, J., Lopez-Alemany, R., Luttun, A., de Lagran, M. M., Diaz, M. A., Jardi, M., Roig, M., Dierssen, M., Dewerchin, M., Carmeliet, P., Munoz-Canoves, P. (2007). uPA deficiency exacerbates muscular dystrophy in MDX mice. JCB 178: 1039-1051 [Abstract] [Full Text]  
• Rouger, K., Fornasari, B., Armengol, V., Jouvion, G., Leroux, I., Dubreil, L., Feron, M., Guevel, L., Cherel, Y. (2007). Progenitor Cell Isolation From Muscle-derived Cells Based on Adhesion Properties. J. Histochem. Cytochem. 55: 607-618 [Abstract] [Full Text]  
• L'honore, A., Rana, V., Arsic, N., Franckhauser, C., Lamb, N. J., Fernandez, A. (2007). Identification of a New Hybrid Serum Response Factor and Myocyte Enhancer Factor 2-binding Element in MyoD Enhancer Required for MyoD Expression during Myogenesis. Mol. Biol. Cell 18: 1992-2001 [Abstract] [Full Text]  
• Dogra, C., Hall, S. L., Wedhas, N., Linkhart, T. A., Kumar, A. (2007). Fibroblast Growth Factor Inducible 14 (Fn14) Is Required for the Expression of Myogenic Regulatory Factors and Differentiation of Myoblasts into Myotubes: EVIDENCE FOR TWEAK-INDEPENDENT FUNCTIONS OF Fn14 DURING MYOGENESIS. J. Biol. Chem. 282: 15000-15010 [Abstract] [Full Text]  
• Cottle, D. L., McGrath, M. J., Cowling, B. S., Coghill, I. D., Brown, S., Mitchell, C. A. (2007). FHL3 binds MyoD and negatively regulates myotube formation. J. Cell Sci. 120: 1423-1435 [Abstract] [Full Text]  
• Zammit, P. S., Partridge, T. A., Yablonka-Reuveni, Z. (2006). The Skeletal Muscle Satellite Cell: The Stem Cell That Came in From the Cold. J. Histochem. Cytochem. 54: 1177-1191 [Abstract] [Full Text]  
• Frank, N. Y., Kho, A. T., Schatton, T., Murphy, G. F., Molloy, M. J., Zhan, Q., Ramoni, M. F., Frank, M. H., Kohane, I. S., Gussoni, E. (2006). Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin. JCB 175: 99-110 [Abstract] [Full Text]  
• Wilson, E. M., Rotwein, P. (2006). Control of MyoD Function during Initiation of Muscle Differentiation by an Autocrine Signaling Pathway Activated by Insulin-like Growth Factor-II. J. Biol. Chem. 281: 29962-29971 [Abstract] [Full Text]  
• Wu, Z., Huang, X., Feng, Y., Handschin, C., Feng, Y., Gullicksen, P. S., Bare, O., Labow, M., Spiegelman, B., Stevenson, S. C. (2006). Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1{alpha} transcription and mitochondrial biogenesis in muscle cells. Proc. Natl. Acad. Sci. USA 103: 14379-14384 [Abstract] [Full Text]  
• Parker, M. H., Perry, R. L. S., Fauteux, M. C., Berkes, C. A., Rudnicki, M. A. (2006). MyoD Synergizes with the E-Protein HEB{beta} To Induce Myogenic Differentiation. Mol. Cell. Biol. 26: 5771-5783 [Abstract] [Full Text]  
• Frock, R. L., Kudlow, B. A., Evans, A. M., Jameson, S. A., Hauschka, S. D., Kennedy, B. K. (2006). Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.. Genes Dev. 20: 486-500 [Abstract] [Full Text]  
• Knapp, J. R., Davie, J. K., Myer, A., Meadows, E., Olson, E. N., Klein, W. H. (2006). Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size. Development 133: 601-610 [Abstract] [Full Text]  
• Hawke, T. J., Kanatous, S. B., Martin, C. M., Goetsch, S. C., Garry, D. J. (2006). Rad is temporally regulated within myogenic progenitor cells during skeletal muscle regeneration. Am. J. Physiol. Cell Physiol. 290: C379-C387 [Abstract] [Full Text]  
• Ishibashi, J., Perry, R. L., Asakura, A., Rudnicki, M. A. (2005). MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions. JCB 171: 471-482 [Abstract] [Full Text]  
• Brack, A. S., Bildsoe, H., Hughes, S. M. (2005). Evidence that satellite cell decrement contributes to preferential decline in nuclear number from large fibres during murine age-related muscle atrophy. J. Cell Sci. 118: 4813-4821 [Abstract] [Full Text]  
• Blais, A., Tsikitis, M., Acosta-Alvear, D., Sharan, R., Kluger, Y., Dynlacht, B. D. (2005). An initial blueprint for myogenic differentiation. Genes Dev. 19: 553-569 [Abstract] [Full Text]  
• Markiewicz, E., Ledran, M., Hutchison, C. J. (2005). Remodelling of the nuclear lamina and nucleoskeleton is required for skeletal muscle differentiation in vitro. J. Cell Sci. 118: 409-420 [Abstract] [Full Text]  
• Kang, J.-S., Yi, M.-J., Zhang, W., Feinleib, J. L., Cole, F., Krauss, R. S. (2004). Netrins and neogenin promote myotube formation. JCB 167: 493-504 [Abstract] [Full Text]  
• Lee, H.-J., Goring, W., Ochs, M., Muhlfeld, C., Steding, G., Paprotta, I., Engel, W., Adham, I. M. (2004). Sox15 Is Required for Skeletal Muscle Regeneration. Mol. Cell. Biol. 24: 8428-8436 [Abstract] [Full Text]  
• Huh, M. S., Parker, M. H., Scime, A., Parks, R., Rudnicki, M. A. (2004). Rb is required for progression through myogenic differentiation but not maintenance of terminal differentiation. JCB 166: 865-876 [Abstract] [Full Text]  
• Zammit, P. S., Golding, J. P., Nagata, Y., Hudon, V., Partridge, T. A., Beauchamp, J. R. (2004). Muscle satellite cells adopt divergent fates: a mechanism for self-renewal?. JCB 166: 347-357 [Abstract] [Full Text]  
• Ishido, M., Kami, K., Masuhara, M. (2004). In vivo expression patterns of MyoD, p21, and Rb proteins in myonuclei and satellite cells of denervated rat skeletal muscle. Am. J. Physiol. Cell Physiol. 287: C484-C493 [Abstract] [Full Text]  
• Vadivelu, S. K., Kurzbauer, R., Dieplinger, B., Zweyer, M., Schafer, R., Wernig, A., Vietor, I., Huber, L. A. (2004). Muscle Regeneration and Myogenic Differentiation Defects in Mice Lacking TIS7. Mol. Cell. Biol. 24: 3514-3525 [Abstract] [Full Text]  
• Storbeck, C. J., Drmanic, S., Daniel, K., Waring, J. D., Jirik, F. R., Parry, D. J., Ahmed, N., Sabourin, L. A., Ikeda, J.-E, Korneluk, R. G. (2004). Inhibition of myogenesis in transgenic mice expressing the human DMPK 3'-UTR. Hum Mol Genet 13: 589-600 [Abstract] [Full Text]  
• Komaki, M., Asakura, A., Rudnicki, M. A., Sodek, J., Cheifetz, S. (2004). MyoD enhances BMP7-induced osteogenic differentiation of myogenic cell cultures. J. Cell Sci. 117: 1457-1468 [Abstract] [Full Text]  
• Li, Y., Foster, W., Deasy, B. M., Chan, Y., Prisk, V., Tang, Y., Cummins, J., Huard, J. (2004). Transforming Growth Factor-{beta}1 Induces the Differentiation of Myogenic Cells into Fibrotic Cells in Injured Skeletal Muscle: A Key Event in Muscle Fibrogenesis. Am. J. Pathol. 164: 1007-1019 [Abstract] [Full Text]  
• Safi, A., Vandromme, M., Caussanel, S., Valdacci, L., Baas, D., Vidal, M., Brun, G., Schaeffer, L., Goillot, E. (2004). Role for the Pleckstrin Homology Domain-Containing Protein CKIP-1 in Phosphatidylinositol 3-Kinase-Regulated Muscle Differentiation. Mol. Cell. Biol. 24: 1245-1255 [Abstract] [Full Text]  
• Vassilakopoulos, T., Petrof, B. J. (2004). Ventilator-induced Diaphragmatic Dysfunction. Am. J. Respir. Crit. Care Med. 169: 336-341 [Full Text]  
• CHARGE, S. B. P., RUDNICKI, M. A. (2004). Cellular and Molecular Regulation of Muscle Regeneration. Physiol. Rev. 84: 209-238 [Abstract] [Full Text]  
• Wilson, E. M., Hsieh, M. M., Rotwein, P. (2003). Autocrine Growth Factor Signaling by Insulin-like Growth Factor-II Mediates MyoD-stimulated Myocyte Maturation. J. Biol. Chem. 278: 41109-41113 [Abstract] [Full Text]  
• Cao, Y., Zhao, Z., Gruszczynska-Biegala, J., Zolkiewska, A. (2003). Role of Metalloprotease Disintegrin ADAM12 in Determination of Quiescent Reserve Cells during Myogenic Differentiation In Vitro. Mol. Cell. Biol. 23: 6725-6738 [Abstract] [Full Text]  
• Wang, Z.-Z., Washabaugh, C. H., Yao, Y., Wang, J.-M., Zhang, L., Ontell, M. P., Watkins, S. C., Rudnicki, M. A., Ontell, M. (2003). Aberrant Development of Motor Axons and Neuromuscular Synapses in MyoD-Null Mice. J. Neurosci. 23: 5161-5169 [Abstract] [Full Text]  
• Pavlath, G. K., Dominov, J. A., Kegley, K. M., Miller, J. B. (2003). Regeneration of Transgenic Skeletal Muscles with Altered Timing of Expression of the Basic Helix-Loop-Helix Muscle Regulatory Factor MRF4. Am. J. Pathol. 162: 1685-1691 [Abstract] [Full Text]  
• Vernon, A. E., Philpott, A. (2003). A single cdk inhibitor, p27Xic1, functions beyond cell cycle regulation to promote muscle differentiation in Xenopus. Development 130: 71-83 [Abstract] [Full Text]  
• Jankowski, R. J., Deasy, B. M., Cao, B., Gates, C., Huard, J. (2002). The role of CD34 expression and cellular fusion in the regeneration capacity of myogenic progenitor cells. J. Cell Sci. 115: 4361-4374 [Abstract] [Full Text]  
• Amack, J. D., Reagan, S. R., Mahadevan, M. S. (2002). Mutant DMPK 3'-UTR transcripts disrupt C2C12 myogenic differentiation by compromising MyoD. JCB 159: 419-429 [Abstract] [Full Text]  
• Asakura, A., Seale, P., Girgis-Gabardo, A., Rudnicki, M. A. (2002). Myogenic specification of side population cells in skeletal muscle. JCB 159: 123-134 [Abstract] [Full Text]  
• Charge, S. B. P., Brack, A. S., Hughes, S. M. (2002). Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy. Am. J. Physiol. Cell Physiol. 283: C1228-C1241 [Abstract] [Full Text]  
• Staib, J. L., Swoap, S. J., Powers, S. K. (2002). Diaphragm contractile dysfunction in MyoD gene-inactivated mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283: R583-R590 [Abstract] [Full Text]  
• Hollnagel, A., Grund, C., Franke, W. W., Arnold, H.-H. (2002). The Cell Adhesion Molecule M-Cadherin Is Not Essential for Muscle Development and Regeneration. Mol. Cell. Biol. 22: 4760-4770 [Abstract] [Full Text]  
• Grounds, M. D., White, J. D., Rosenthal, N., Bogoyevitch, M. A. (2002). The Role of Stem Cells in Skeletal and Cardiac Muscle Repair. J. Histochem. Cytochem. 50: 589-610 [Abstract] [Full Text]  
• Andree, B., Fleige, A., Arnold, H.-H., Brand, T. (2002). Mouse Pop1 Is Required for Muscle Regeneration in Adult Skeletal Muscle. Mol. Cell. Biol. 22: 1504-1512 [Abstract] [Full Text]  
• Amack, J. D., Mahadevan, M. S. (2001). The myotonic dystrophy expanded CUG repeat tract is necessary but not sufficient to disrupt C2C12 myoblast differentiation. Hum Mol Genet 10: 1879-1887 [Abstract] [Full Text]  
• Launay, T., Armand, A.-S., Charbonnier, F., Mira, J.-C., Donsez, E., Gallien, C. L., Chanoine, C. (2001). Expression and Neural Control of Myogenic Regulatory Factor Genes During Regeneration of Mouse Soleus. J. Histochem. Cytochem. 49: 887-900 [Abstract] [Full Text]  
• Oldham, J. M., Martyn, J. A. K., Sharma, M., Jeanplong, F., Kambadur, R., Bass, J. J. (2001). Molecular expression of myostatin and MyoD is greater in double-muscled than normal-muscled cattle fetuses. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280: R1488-R1493 [Abstract] [Full Text]  
• Torrente, Y., Tremblay, J.-P, Pisati, F., Belicchi, M., Rossi, B., Sironi, M., Fortunato, F., El Fahime, M., D'Angelo, M. G., Caron, N. J., Constantin, G., Paulin, D., Scarlato, G., Bresolin, N. (2001). Intraarterial Injection of Muscle-Derived Cd34+Sca-1+ Stem Cells Restores Dystrophin in mdx Mice. JCB 152: 335-348 [Abstract] [Full Text]  
• White, J. D., Scaffidi, A., Davies, M., McGeachie, J., Rudnicki, M. A., Grounds, M. D. (2000). Myotube Formation is Delayed but not Prevented in MyoD-deficient Skeletal Muscle: Studies in Regenerating Whole Muscle Grafts of Adult Mice. J. Histochem. Cytochem. 48: 1531-1544 [Abstract] [Full Text]  
• Adams, G. R., Haddad, F., Baldwin, K. M. (1999). Time course of changes in markers of myogenesis in overloaded rat skeletal muscles. J. Appl. Physiol. 87: 1705-1712 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents