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PMID: 10037786 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Reduced differentiation potential of primary MyoD-/- myogenic cells derived from adult skeletal muscle.

The Journal of cell biology ·Vol. 144 ·No. 4 ·1999-02-22 ·Pages 631-43

Sabourin LA, Girgis-Gabardo A, Seale P, Asakura A, Rudnicki MA

Abstract

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.

MeSH Terms
Animals Cell Differentiation Cell Division Cells, Cultured Gene Expression Lac Operon Mice Mice, Knockout Muscle, Skeletal/cytology,physiology MyoD Protein/genetics,physiology Phenotype Proto-Oncogene Proteins c-met/metabolism RNA, Messenger/genetics,metabolism Regeneration/genetics,physiology
Chemicals
MyoD Protein RNA, Messenger Proto-Oncogene Proteins c-met
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sabourin L A
Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
Girgis-Gabardo A
Seale P
Asakura A
Rudnicki M A
References (58)
58 references, click to expand
  1. Migration of myogenic cells in the rat extensor digitorum longus muscle studied with a split autograft model.
    Cell Tissue Res. 1990 Oct;262(1):81-8 PMID: 2257618
  2. Integrin and cadherin synergy regulates contact inhibition of migration and motile activity.
    J Cell Biol. 1998 Apr 20;141(2):515-26 PMID: 9548728
  3. Insulin-like growth factor I rapidly induces tyrosine phosphorylation of a Mr 150,000 and a Mr 160,000 protein in highly metastatic mouse colon carcinoma 26 NL-17 cells.
    Cancer Res. 1991 Nov 1;51(21):5859-65 PMID: 1718586
  4. Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells.
    Genes Dev. 1992 Mar;6(3):481-96 PMID: 1547944
  5. Plakoglobin and beta-catenin: distinct but closely related.
    Science. 1992 Aug 21;257(5073):1142-4 PMID: 1509266
  6. Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death.
    Cell. 1992 Oct 30;71(3):369-82 PMID: 1423602
  7. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development.
    Cell. 1992 Oct 30;71(3):383-90 PMID: 1330322
  8. Interplay between proliferation and differentiation within the myogenic lineage.
    Dev Biol. 1992 Dec;154(2):261-72 PMID: 1330787
  9. In vitro and in vivo expression of alpha 7 integrin and desmin define the primary and secondary myogenic lineages.
    Dev Biol. 1993 Mar;156(1):209-29 PMID: 8449367
  10. Myogenin gene disruption results in perinatal lethality because of severe muscle defect.
    Nature. 1993 Aug 5;364(6437):532-5 PMID: 8393146
  11. Overexpression of the human type-1 insulin-like growth factor receptor in rat L6 myoblasts induces ligand-dependent cell proliferation and inhibition of differentiation.
    Exp Cell Res. 1993 Oct;208(2):504-8 PMID: 8375479
  12. PEA3 is overexpressed in mouse metastatic mammary adenocarcinomas.
    Oncogene. 1993 Nov;8(11):3037-42 PMID: 7692372
  13. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
    Cell. 1993 Nov 19;75(4):805-16 PMID: 8242751
  14. WAF1, a potential mediator of p53 tumor suppression.
    Cell. 1993 Nov 19;75(4):817-25 PMID: 8242752
  15. MyoD or Myf-5 is required for the formation of skeletal muscle.
    Cell. 1993 Dec 31;75(7):1351-9 PMID: 8269513
  16. Temporal expression of myogenic regulatory genes during activation, proliferation, and differentiation of rat skeletal muscle satellite cells.
    J Cell Physiol. 1994 May;159(2):379-85 PMID: 8163577
  17. Temporal expression of regulatory and structural muscle proteins during myogenesis of satellite cells on isolated adult rat fibers.
    Dev Biol. 1994 Aug;164(2):588-603 PMID: 7913900
  18. Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.
    Cell. 1994 Aug 26;78(4):625-33 PMID: 8069911
  19. Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles.
    Dev Dyn. 1994 Apr;199(4):326-37 PMID: 8075434
  20. IGF-II is more active than IGF-I in stimulating L6A1 myogenesis: greater mitogenic actions of IGF-I delay differentiation.
    J Cell Physiol. 1994 Nov;161(2):277-84 PMID: 7962112
  21. Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase.
    Science. 1995 Feb 17;267(5200):1022-4 PMID: 7863328
  22. Muscle regeneration following injury can be modified in vivo by immune neutralization of basic fibroblast growth factor, transforming growth factor beta 1 or insulin-like growth factor I.
    J Neuroimmunol. 1995 Mar;57(1-2):85-91 PMID: 7706442
  23. The MyoD family of transcription factors and skeletal myogenesis.
    Bioessays. 1995 Mar;17(3):203-9 PMID: 7748174
  24. MyoD-induced expression of p21 inhibits cyclin-dependent kinase activity upon myocyte terminal differentiation.
    Mol Cell Biol. 1995 Jul;15(7):3823-9 PMID: 7791789
  25. Inactivation of the myogenic bHLH gene MRF4 results in up-regulation of myogenin and rib anomalies.
    Genes Dev. 1995 Jun 1;9(11):1388-99 PMID: 7797078
  26. Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome.
    Development. 1995 Oct;121(10):3347-58 PMID: 7588068
  27. Hepatocyte growth factor activates quiescent skeletal muscle satellite cells in vitro.
    J Cell Physiol. 1995 Nov;165(2):307-12 PMID: 7593208
  28. Involvement of M-cadherin in terminal differentiation of skeletal muscle cells.
    J Cell Sci. 1995 Sep;108 ( Pt 9):2973-81 PMID: 8537437
  29. Cloning and expression of the Rb-related mouse p130 mRNA.
    Oncogene. 1996 Apr 4;12(7):1433-40 PMID: 8622859
  30. MyoD is required for myogenic stem cell function in adult skeletal muscle.
    Genes Dev. 1996 May 15;10(10):1173-83 PMID: 8675005
  31. The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo.
    Cell. 1996 May 17;85(4):501-12 PMID: 8653786
  32. Rapid death of injected myoblasts in myoblast transfer therapy.
    Muscle Nerve. 1996 Jul;19(7):853-60 PMID: 8965839
  33. Dissection of the ability of the chicken lysozyme gene 5' matrix attachment region to stimulate transgene expression and to dampen position effects.
    Biochemistry. 1996 Aug 20;35(33):10735-42 PMID: 8718863
  34. Determination versus differentiation and the MyoD family of transcription factors.
    Biochem Cell Biol. 1995 Sep-Oct;73(9-10):723-32 PMID: 8714693
  35. Signal transduction through beta-catenin and specification of cell fate during embryogenesis.
    Genes Dev. 1996 Oct 15;10(20):2527-39 PMID: 8895655
  36. Proliferation precedes differentiation in IGF-I-stimulated myogenesis.
    J Cell Biol. 1996 Oct;135(2):431-40 PMID: 8896599
  37. Autonomous differentiation in the mouse myogenic cell line, C2, involves a mutual positive control between insulin-like growth factor II and MyoD, operating as early as at the myoblast stage.
    J Cell Sci. 1996 Mar;109 ( Pt 3):551-60 PMID: 8907701
  38. Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes.
    J Cell Sci. 1996 Dec;109 ( Pt 13):3013-23 PMID: 9004036
  39. Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro.
    J Cell Biol. 1982 Dec;95(3):763-70 PMID: 6185504
  40. Emergence of TPA-resistant 'satellite' cells during muscle histogenesis of human limb.
    Exp Cell Res. 1985 Oct;160(2):403-11 PMID: 3899691
  41. Rapid extraction of high molecular weight RNA from cultured cells and granulocytes for Northern analysis.
    Nucleic Acids Res. 1988 Feb 25;16(4):1487-97 PMID: 2450333
  42. The expression of sarcomeric muscle-specific contractile protein genes in BC3H1 cells: BC3H1 cells resemble skeletal myoblasts that are defective for commitment to terminal differentiation.
    J Cell Biol. 1989 May;108(5):1799-806 PMID: 2715180
  43. Aberrant regulation of MyoD1 contributes to the partially defective myogenic phenotype of BC3H1 cells.
    J Cell Biol. 1990 Apr;110(4):929-37 PMID: 1691195
  44. Migration of myoblasts across basal lamina during skeletal muscle development.
    Nature. 1990 May 24;345(6273):350-3 PMID: 2111464
  45. Myogenic programs of mouse muscle cell lines: expression of myosin heavy chain isoforms, MyoD1, and myogenin.
    J Cell Biol. 1990 Sep;111(3):1149-59 PMID: 2167895
  46. Developmental regulation of M-cadherin in the terminal differentiation of skeletal myoblasts.
    Dev Dyn. 1994 Aug;200(4):305-12 PMID: 7994077
  47. Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD.
    Science. 1995 Feb 17;267(5200):1018-21 PMID: 7863327
  48. New functional activities for the p21 family of CDK inhibitors.
    Genes Dev. 1997 Apr 1;11(7):847-62 PMID: 9106657
  49. Overexpression of the integrin-linked kinase promotes anchorage-independent cell cycle progression.
    J Biol Chem. 1997 May 23;272(21):13937-44 PMID: 9153256
  50. Transcription factor polyomavirus enhancer activator protein 3 (PEA3) is induced in adult rats following muscle injury.
    J Nutr. 1997 May;127(5 Suppl):1007S-1010S PMID: 9164285
  51. Mouse adhalin: primary structure and expression during late stages of muscle differentiation in vitro.
    Biochem Biophys Res Commun. 1997 Jun 9;235(1):227-35 PMID: 9196068
  52. A role for the ETS domain transcription factor PEA3 in myogenic differentiation.
    Mol Cell Biol. 1997 Sep;17(9):5550-8 PMID: 9271430
  53. The fate of individual myoblasts after transplantation into muscles of DMD patients.
    Nat Med. 1997 Sep;3(9):970-7 PMID: 9288722
  54. Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways.
    Curr Opin Cell Biol. 1997 Oct;9(5):683-90 PMID: 9330872
  55. Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells.
    Dev Biol. 1997 Nov 15;191(2):270-83 PMID: 9398440
  56. MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle.
    Development. 1997 Dec;124(23):4729-38 PMID: 9428409
  57. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4374-9 PMID: 9539744
  58. The myoD gene family: nodal point during specification of the muscle cell lineage.
    Science. 1991 Feb 15;251(4995):761-6 PMID: 1846704
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.144.4.631
Published
1999-02-22
Pages
631-43
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2132931
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.144.4.631 PMC Full Text View journal details
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