Factors Influencing Satellite Cell Activity during Skeletal Muscle Development in Avian and Mammalian Species

  • Nierobisz, Lidia S (Department of Poultry Science, College of Agriculture and Life Sciences North Carolina State University) ;
  • Mozdziak, Paul E (Department of Poultry Science, College of Agriculture and Life Sciences North Carolina State University)
  • Received : 2007.02.10
  • Accepted : 2007.07.28
  • Published : 2008.03.01


Avian and mammalian skeletal muscles exhibit a remarkable ability to adjust to physiological stressors induced by growth, exercise, injury and disease. The process of muscle recovery following injury and myonuclear accretion during growth is attributed to a small population of satellite cells located beneath the basal lamina of the myofiber. Several metabolic factors contribute to the activation of satellite cells in response to stress mediated by illness, injury or aging. This review will describe the regenerative properties of satellite cells, the processes of satellite cell activation and highlight the potential role of satellite cells in skeletal muscle growth, tissue engineering and meat production.


  1. Adams, G. R., F. Haddad and K. M. Baldwin. 1999. Time course of changes in markers of myogenesis in overloaded rat skeletal muscles. J. Appl. Physiol. 87:1705-1712.
  2. Allbrook, D. B., M. F. Han and A. E. Hellmuth. 1971. Population of muscle satellite cells in relation to age and mitotic activity Pathol. 3:233.
  3. Allen, R. E. and L. K. Boxhorn. 1989. Regulation of skeletal muscle satellite cell proliferation and differentiation by transforming growth factor-beta, insulin-like growth factor I, and fibroblast growth factor. J. Cell. Physiol. 138:311-315.
  4. Allen, R. E., S. M. Sheehan, R. G. Taylor, T. L. Kendall and G. M. Rice. 1995. Hepatocyte growth factor activates quiescent skeletal muscle satellite cells in vitro. J. Cell. Physiol. 165: 307-312.
  5. Ascadi, G., G. Dickson, D. R. Love, A. Jani, F. S Walsh, A. Gurusinghe, J. A. Wolff and K. E. Davies. 1991. Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature 352:815-818.
  6. Asmundson, V. S. and L. M. Julian. 1956. Inherited muscle abnormality in the domestic fowl. J. Hered. 47:248-252.
  7. Bach, A. D., J. P. Beier and R. E. Horch. 2004. Skeletal muscle tissue engineering. J. Cell. Mol. Med. 8:413-422.
  8. Bischoff, R. 1986. Proliferation of muscle satellite cells on intact myofibers in culture. Dev. Biol. 115:129-139.
  9. Blau, H. M., T. R. Brazelton and J. M. Weimann. 2001. The evolving concept of a stem cell: entity or function? Cell 105:829-841.
  10. Bonassar, L. J. and C. A. Vacanti. 1998. Tissue engineering: the first decade and beyond. J. Cell. Biochem. 30-31:297-303.
  11. Bondesen, B. A., S. T. Mills, K. M. Kegley and G. K. Pavlath. 2004. The COX2 pathway is essential during early stages of skeletal muscle regeneration. Am. J. Physiol. Cell. Physiol. 287:C475-C483.
  12. Borisov, A. B., E. I. Dedkov and B. M. Carlson. 2005. Differentiation of activated satellite cells in denervated muscle following single fusions in situ and in cell culture. Histochem. Cell. Biol. 124:13-23.
  13. Carlson, B. M. and J. A. Faulkner. 1988. Reinnervation of longterm denervated muscle freely grafted into an innervated limb. Exp. Neurol. 102:50-56.
  14. Carlson, B. M. and J. A. Faulkner. 1989. Muscle transplantation between young and old rats: age of host determines recovery. Am. J. Physiol. 256:C1262-1266.
  15. Carson, J. A. and S. E. Alway. 1996. Stretch overload-induced satellite cell activation in slow tonic muscle from adult and aged Japanese quail. Am. J. Physiol. 270:C578-C584.
  16. Charge, S. B. and M. A. Rudnicki. 2004. Cellular and molecular regulation of muscle regeneration. Physiol. Rev. 84:209-238.
  17. Cohn, R. D., M. D. Henry, D. E. Michele, R. Barresi, F. Saito, S. A. Moore, J. D. Flanagan, M. W. Skwarchuk, M. E. Robbins, J. R. Mendell, C. A. Collins, I. Olsen, P. S. Zammit, L. Heslop, A. Petrie, T. A. Partridge and J. E. Morgan. 2005. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122:289-301.
  18. Conboy, I. M. and T. A. Rando. 2002. The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev. Cell 2:397-409.
  19. Conboy, I. M., M. J. Conboy, G. M. Smythe and T. A. Rando. 2003. Notch-mediated restoration of regenerative potential to aged muscle. Sci. 302:1575-1577.
  20. Conboy, I. M., M. J. Conboy, A. J. Wagers, E. R. Girma, I. L. Weissman and T. A. Rando. 2005. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760-764.
  21. Coolican, S. A., D. S. Samuel, D. Z. Ewton, F. J. McWade, and J. R. Florini. 1997. The mitogenic and myogenic actions of insulin-like growth factors utilize distinct signaling pathways. J. Biol. Chem. 272:6653-6662.
  22. Cote, P. D., H. Moukles, M. Lindenbaum and S. Carbonetto. 1999. Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses. Nat. Genet. 23:338-342.
  23. Dangott, B., E. Schultz and P. E. Mozdziak. 2000. Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int. J. Sports Med. 21:13-16.
  24. Darr, K. C. and E. Schultz. 1987. Exercise-induced satellite cell activation in growing and mature skeletal muscle. J. Appl. Physiol. 63:1816-1821.
  25. Dedkov, E. L., T. Y. Kostrominova, A. B. Borisov and B. M. Carlson. 2001. Reparative myogenesis in long-term denervated skeletal muscles of adult rats results in a reduction of the satellite cell population. Anat. Rec. 263:139-154.
  26. Gibson, M. C. and E. Schultz. 1983. Age-related differences in absolute numbers of skeletal muscle satellite cells. Muscle Nerve. 6:574-580.
  27. Gorospe, J. R. M., M. D. Tharp, J. Hinckley, J. N. Kornegay and E. P. Hoffman. 1994. A role for mast-cells in the progression of Duchenne Muscular-Dystrophy- correlations in dystrophindeficient humans, dogs, and mice. J. Neurol. Sci. 122:44-56.
  28. Greene, E. A. and R. E. Allen. 1991. Growth factor regulation of bovine satellite cell growth in vitro. J. Anim. Sci. 69:146-152.
  29. Halevy, O., Y. Plestun, M. Z. Allouh, B. W. C. Rosser, Y. Rinkevich, R. Reshef, I. Rozenboim, M. Wieklinski-Lee and Z. Yablonka-Reuveni. 2004. Pattern of Pax7 expression during myogenesis in the posthatch chicken establishes a model for satellite cell differentiation and renewal. Dev. Dyn. 231:489-502.
  30. Hawke, J. T. and D. J. Garry. 2001. Myogenic satellite cells: physiology to molecular biology. J. Appl. Physiol. 91:534-551.
  31. Imamura, M., K. Araishi, S. Noguchi and S. Ebashi. 2000. A sarcoglycan-dystroglycan complex anchors Dp116 and utrophin in the peripheral nervous system. Hum. Mol. Gen. 9:3091-100.
  32. Iwata, Y., Y. Pan, H. Hanada, T. Yoshida and M. Shigekawa. 1996. Dystrophin-glycoprotein complex purified from hamster cardiac muscle. Comparison of the complexes from cardiac and skeletal muscles of hamster and rabbit. J. Mol. Cell Cardiol. 28:2501-2509.
  33. Jin, E.-J., I. Kim, C. Y. Lee and B. C. Park. 2006. Suppressed cell proliferation and differentiation following an over-expression of myostatin is associated with inhibited expression of insulinlike growth factor II and myogenin in rat L6 myoblasts. Asian- Aust. J. Anim. Sci. 19:1508-1513.
  34. Kami, K. and E. Senba. 1998. Localization of leukemia inhibitory factor and interleukin-6 messenger ribonucleic acids in regenerating rat skeletal muscle. Muscle Nerve 21:819-822.<819::AID-MUS20>3.0.CO;2-M
  35. Katagiri, T., S. Akiyama, M. Namiki, M. Komaki, A. Yamaguchi, V. Rosen, M. Wozney, A. Fujisawa-Sehara and T. Suda. 1997. Bone morphogenic protein-2 inhibits terminal differentiation of myogenic cells by suppressing the transcriptional activity of MyoD and myogenin. Exp. Cell. Res. 230:342-351.
  36. King, B. D. and R. K. Entrikin. 1991. Thyroidal involvement in the expression of avian muscular dystrophy. Life. Sci. 48:909-916.
  37. Kocamis, H., D. C. McFarland and J. Killefer. 2001. Terminal expression of growth factor genes during myogenesis of satellite cells derived from the biceps femoris and pectoralis major muscles of the chicken. J. Cell Physiol. 186:146-152.<146::AID-JCP1014>3.0.CO;2-Q
  38. Kurek, J. B., J. J. Bower, M. Romanella, F. Koentgen, M. Murphy and L. Ausitn. 1997. The role of leukemia inhibitory factor in skeletal muscle regeneration. Muscle Nerve, 20:815-822.<815::AID-MUS5>3.0.CO;2-A
  39. LeRoith, D., M. McGuinness, J. Shemer, B. Stannard, F. Lanau, T. N. Faria, H. Kato, H. Werner, M. Adamo and C. T. Roberts. 1992. Insulin-like growth factors. Biol. Signals 1:173-181.
  40. Lescaudron, L. E. Peltekian, J. Fontaine-Perus, D. Paulin, M. Zampieri, L. Garcia and E. Parrish. 1999. Blood borne macrophages are essential for the triggering of muscle regeneration following muscle transplant. Neuromuscul. Disord. 9:72-80.
  41. Mansouri, A., G. Goudreau and P. Gruss. 1999. Pax genes and their role in organogenesis. Cancer Res. 59:1707-1710.
  42. Martin, J. F., L. Li and E. N. Olson. 1992. Repression of Myogenin function by TGF-$\beta$1 is targeted at the basic helixloop- helix motif and is independent of E2A products. J. Biol. Chem. 267:10956-10960.
  43. Marzaro, M., M. T. Conconi, L. Perin, S. Giuliani, P. Gomba, P. De Coppi, G. P. Perrino, P. P. Parnigotto and G. G. Nurssdorfer. 2002. Autologous satellite cell seeding improves in vivo biocompatibility of homologous muscle acellular matrix implants. Int. J. Mol. Med. 10:177-182.
  44. McFarland, D. C., X. Liu, S. G. Velleman, C. Zeng, C. S. Coy and J. E. Pesall. 2003. Variation in fibroblast growth factor response and heparin sulfate proteoglycan production in satellite cell populations. Comp. Biochem. Physiol. 134:341- 351.
  45. Megeney, L. A., B. Kablar, K. Garrett, J. E. Anderson and M. A. Rudnicki. 1996. MyoD is required for myogenic stem cell function in adult skeletal muscle. Genes. Dev. 10:1173-1183.
  46. Miller, K. J., D. Thaloor, S. Matteson and G. K. Paviath. 2000. Hepatocyte growth factor affects satellite cell activation and differentiation in regenerating skeletal muscle. Am. J. Physiol. Cell. Physiol. 287:C174-C181.
  47. Minshall, R. D., D. C. McFarland and M. E. Doumit. 1990. Interaction of insulin-like growth factor I with turkey satellite cells and satellite cell-derived myotubes. Domest. Anim. Endocrinol. 7:413-424.
  48. Moss, F. P. and C. P. Leblond. 1970. Nature of dividing nuclei in skeletal muscle of growing rats. J. Cell. Biol. 44:459-462.
  49. Mozdziak, P. E., E. Schultz and R. G. Cassens. 1994. Satellite cell mitotic-activity in posthatch turkey skeletal-muscle growth. Poult. Sci. 73:547-555.
  50. Mozdziak, P. E, E. Schultz and R. G. Cassens. 1997. Myonuclear accretion is a major determinant of avian skeletal muscle growth. Am. J. Physiol. Cell. Physiol. 272:C565-C571.
  51. Mozdziak, P. E., P. M. Pulvermacher and E. Schultz. 2000. Unloading of juvenile muscle results in a reduced muscle size 9 wk after reloading. J. Appl. Physiol. 88:158-164.
  52. Musaro, A., K. McCullagh, A. Paul, L. Houghton, G. Dobrowolny, M. Molinaro, E. R Barton, H. L. Sweeney and N. Rosenthal. 2001. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat. Genet. 27:195-200.
  53. Nara, H., D. Yoshizawa, H. Aso and T. Yamaguchi. 2001. Bovine myoblast differentiation during the myogenesis. Asian-Aust. J. Anim. Sci. 14:100-105.
  54. Pavlath, G. 1996. Isolation, purification and growth of skeletal muscle cells. In: Methods of Molecular Medicine: Human Cell Culture Protocols (Ed. G. E. Jones). Totawa, NJ, USA. pp. 307-318.
  55. Pophal, S., P. E. Mozdziak and S. L. Vieira. 2004. Satellite cell mitotic activity of broilers fed differing levels of lysine. Int. J. Poult. Sci. 3:758-763.
  56. Saito, F., M. Blank, M. Schroder, H. Manya, T. Shimizu, K. Campbell, T. Endo, M. Mizutani, S. Kroger and K. Matsumura. 2005. Aberrant glycosylation of alpha-Dystroglycan causes defective binding of laminin in the muscle of chicken Muscular Dystrophy. FEBS Letters 579:2359-2363.
  57. Sakuma, K., K. Watenabe, M. Sano, S. Kitajima, K. Sakamoto, I. Uramoto and T. Totsuka. 2000. The adaptive response of transforming growth factor-$\beta$2 and -$\beta$RII in the overloaded, regenerating and denervated muscles of rats. Acta. Neuropathol. 99:177-185.
  58. Schultz, E. and K. M. McCormick. 2000. Skeletal muscle satellite cells. Rev. Physiol. Biochem. Pharmacol. 123:213-257.
  59. Seale, P., L. A. Sabourin, A. Girgis-Gabardo, A. Mansouri, P. Gruss and M. A. Rudnicki. 2000. Pax7 is required for the specification of myogenic satellite cells. Cell 102:777-786.
  60. Seale, P., A. Asakura and M. A. Rudnicki. 2001. The potential of muscle stem cells. Dev. Cell 1:333-342.
  61. Sheenan, S. M. and R. E. Allen. 1999. Skeletal muscle satellite cell proliferation in response to members of the fibroblast growth factor family and hepatocyte growth factor. J. Cell. Physiol. 181:499-506.<499::AID-JCP14>3.0.CO;2-1
  62. Sherwood, R. I., J. L. Christensen, I. M. Conboy, M. J. Conboy, T. A. Rando, I. L. Weissman and A. J. Wagers. 2004. Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119:543-554.
  63. Singh, N. K., H. S. Chae, I. H. Hwang, Y. M. Yoo, C. N. Ahn, H. J. Lee, H. J. Park and H. Y. Chung. 2007. 2, 4- thiazolidindion induced plasticity of myoblast (C2C12) and satellite cells (porcine) - a comparative study. Asian-Aust. J. Anim. Sci. 20:1115-1119.
  64. Tatsumi, R., J. E. Anderson, C. J. Nevoret, O. Halevy and R. E. Allen. 1998. HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells. Dev. Biol. 194:114-128.
  65. Tidball, J. G. 2006. Inflammatory processes in muscle injury and repair. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288:R345-R353.
  66. Viguie, C. A., D. X. Lu, S. K. Huang, H. Rengen and B. M. Carlson. 1997. Quantitative study of the effects of long-term denervation on the extensor digitorum longus muscle of the rat. Anat. Rec. 248:346-354.<346::AID-AR7>3.0.CO;2-N
  67. Wagers, A. J. and I. Weissman. 2004. Stem cell plasticity. Cell 116:639-648.
  68. Wagers, A. J. and I. M. Conboy. 2005. Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell 122:659-667.
  69. Webster, C. and H. M. Blau. 1990 Accelerated age-related decline in replicative life-span of Duchenne muscular dystrophy myoblasts: implications for cells and gene therapy. Somat. Cell. Mol. Genet. 16:557-565.
  70. Wakeford, S., D. J. Watt and T. A. Partridge. 1991. X-irradiation improves mdx mouse muscle as a model of myofiber loss in DMD. Muscle Nerve 14:42-50.
  71. Williamson, R. A. and K. P. Campbell. 2002. Disruption of Dag1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration. Cell 110:639-648.
  72. Yablonka-Reuveni, Z. and B. Paterson. 2001. MyoD and myogenin expression patterns in cultures of fetal and adult chicken myoblasts. J. Histochem. Cytochem. 49:455-462.
  73. Yablonka-Reuveni, Z. and J. E. Anderson. 2006. Satellite cells from dystrophic (Mdx) mice display accelerated differentiation in primary cultures and in isolated myofibers. Dev. Dyn. 235:203-212.
  74. Zammit, P. S., J. P. Golding, Y. Nagata, V. Hudon, T. A. Partridge and J. R. Beauchamp. 2004. Muscle satellite cells adopt divergent fates: a mechanism for self-renewal? J. Cell. Biol. 166:347-357.
  75. Zentella, A. and J. Massague. 1992. Transforming growth factor beta induces myoblast differentiation in the presence of mitogens. Proc. Natl. Acad. Sci. USA 89:5176-5180.