myogenic regulatory factor 5


Summary: A SKELETAL MUSCLE-specific transcription factor that contains a basic HELIX-LOOP-HELIX MOTIF. It plays an essential role in MUSCLE DEVELOPMENT.

Top Publications

  1. Sanchez Gurmaches J, Hung C, Sparks C, Tang Y, Li H, Guertin D. PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab. 2012;16:348-62 pubmed
    ..Thus, the spectrum of adipocytes arising from Myf5(+) precursors is broader than previously thought, and differences in PI3K activity between adipocyte lineages alter body fat distribution. ..
  2. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454:961-7 pubmed publisher
    ..Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis. ..
  3. Rudnicki M, Schnegelsberg P, Stead R, Braun T, Arnold H, Jaenisch R. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell. 1993;75:1351-9 pubmed
  4. Relaix F, Polimeni M, Rocancourt D, Ponzetto C, Schafer B, Buckingham M. The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo. Genes Dev. 2003;17:2950-65 pubmed
    ..This gain-of-function allele provides a new approach to the molecular and cellular analysis of the role of Pax3 and of its target genes in vivo. ..
  5. Block N, Zhu Z, Kachinsky A, Dominov J, Miller J. Acceleration of somitic myogenesis in embryos of myogenin promoter-MRF4 transgenic mice. Dev Dyn. 1996;207:382-94 pubmed
    ..MRF function, therefore, appears to be differentially regulated in dermatomal and myotomal cells. ..
  6. Tajbakhsh S, Borello U, Vivarelli E, Kelly R, Papkoff J, Duprez D, et al. Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5. Development. 1998;125:4155-62 pubmed
  7. Shi D, Bourdelas A, Umbhauer M, Boucaut J. Zygotic Wnt/beta-catenin signaling preferentially regulates the expression of Myf5 gene in the mesoderm of Xenopus. Dev Biol. 2002;245:124-35 pubmed
    ..These results suggest that Wnt/beta-catenin pathway is required for regulating myogenic gene expression in the presumptive mesoderm. In particular, it may directly activate the expression of the XMyf5 gene in the muscle precursor cells. ..
  8. Sambasivan R, Gayraud Morel B, Dumas G, Cimper C, Paisant S, Kelly R, et al. Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Dev Cell. 2009;16:810-21 pubmed publisher
    ..These findings identify novel genetic networks that may provide insights into myopathies which often affect only subsets of muscles...
  9. Giordani J, Bajard L, Demignon J, Daubas P, Buckingham M, Maire P. Six proteins regulate the activation of Myf5 expression in embryonic mouse limbs. Proc Natl Acad Sci U S A. 2007;104:11310-5 pubmed
    ..Six homeoproteins, which also directly regulate the myogenic differentiation gene Myogenin and lie genetically upstream of Pax3, thus control hypaxial myogenesis at multiple levels. ..

More Information


  1. Ye H, Chen S, Xu J. Molecular cloning and characterization of the Myf5 gene in sea perch (Lateolabrax japonicus). Comp Biochem Physiol B Biochem Mol Biol. 2007;147:452-9 pubmed
    ..Further, Myf5 mRNA was expressed in several sea perch cell lines such as LJES1, LJHK, LJH-1, LJH-2, LJS, LJL, although its expression level varied greatly among different cell lines. ..
  2. Bajanca F, Luz M, Raymond K, Martins G, Sonnenberg A, Tajbakhsh S, et al. Integrin alpha6beta1-laminin interactions regulate early myotome formation in the mouse embryo. Development. 2006;133:1635-44 pubmed
    ..Engagement of laminin by alpha6beta1 also plays a role in maintaining the undifferentiated state of cells in the dermomyotome prior to their entry into the myotome. ..
  3. Ishibashi J, Perry R, Asakura A, Rudnicki M. MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions. J Cell Biol. 2005;171:471-82 pubmed
    ..Together, these results support the notion that Myf5 functions toward myoblast proliferation, whereas MyoD prepares myoblasts for efficient differentiation. ..
  4. Geetha Loganathan P, Nimmagadda S, Prols F, Patel K, Scaal M, Huang R, et al. Ectodermal Wnt-6 promotes Myf5-dependent avian limb myogenesis. Dev Biol. 2005;288:221-33 pubmed
    ..One of the signals is Wnt-6, which plays a unique role in promoting limb myogenesis via Pax3/Paraxis-Myf5, whereas the other putative signaling pathway involving MyoD expression is negatively regulated by Wnt-6 signaling. ..
  5. Buckingham M. Skeletal muscle formation in vertebrates. Curr Opin Genet Dev. 2001;11:440-8 pubmed
  6. Borycki A, Brunk B, Tajbakhsh S, Buckingham M, Chiang C, Emerson C. Sonic hedgehog controls epaxial muscle determination through Myf5 activation. Development. 1999;126:4053-63 pubmed
  7. Langlands K, Yin X, Anand G, Prochownik E. Differential interactions of Id proteins with basic-helix-loop-helix transcription factors. J Biol Chem. 1997;272:19785-93 pubmed
    ..The Id proteins thus display a signature range of interactions with all of their potential dimerization partners and may play a role in myogenesis which is distinct from that in hematopoiesis. ..
  8. Tajbakhsh S, Rocancourt D, Buckingham M. Muscle progenitor cells failing to respond to positional cues adopt non-myogenic fates in myf-5 null mice. Nature. 1996;384:266-70 pubmed
    ..In its absence, muscle progenitors, having activated myf-5, remain multipotent and differentiate into other somitic derivatives according to their local environment. ..
  9. Hadchouel J, Tajbakhsh S, Primig M, Chang T, Daubas P, Rocancourt D, et al. Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo. Development. 2000;127:4455-67 pubmed
    ..Such regulatory heterogeneity may underlie the observed restriction of myopathies to particular muscle subgroups. ..
  10. Bajard L, Relaix F, Lagha M, Rocancourt D, Daubas P, Buckingham M. A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly activates Myf5 in muscle progenitor cells in the limb. Genes Dev. 2006;20:2450-64 pubmed
    ..Mutation of the Pax3 site abolishes all expression controlled by the 145-bp sequence in transgenic mouse embryos. We conclude that Pax3 directly regulates Myf5 in the hypaxial somite and its derivatives. ..
  11. Chen Y, Lee W, Liu C, Tsai H. Molecular structure, dynamic expression, and promoter analysis of zebrafish (Danio rerio) myf-5 gene. Genesis. 2001;29:22-35 pubmed
    ..Results showed that a small, 82 bp (nucleotide positions from -82 to -1), regulatory cassette is sufficient to control the somite- and stage-specific expression of zebrafish myf-5 during early development. ..
  12. Beauchamp J, Heslop L, Yu D, Tajbakhsh S, Kelly R, Wernig A, et al. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J Cell Biol. 2000;151:1221-34 pubmed
    ..We conclude that the expression of CD34, Myf5, and M-cadherin defines quiescent, committed precursors and speculate that the CD34(-ve), Myf5(-ve) minority may be involved in maintaining the lineage-committed majority. ..
  13. Lin G, Geng X, Chen Y, Qu B, Wang F, Hu R, et al. T-box binding site mediates the dorsal activation of myf-5 in Xenopus gastrula embryos. Dev Dyn. 2003;226:51-8 pubmed
    ..The T-box binding site could be bound by and respond to T-box proteins. T-box genes could induce Xmyf-5. The results suggest that T-box proteins are involved in the specification of myogenic mesoderm and muscle development. ..
  14. Tan X, Zhang Y, Zhang P, Xu P, Xu Y. Molecular structure and expression patterns of flounder (Paralichthys olivaceus) Myf-5, a myogenic regulatory factor. Comp Biochem Physiol B Biochem Mol Biol. 2006;145:204-13 pubmed
    ..In the hatching stage, the expression was also detected in other muscle cells such as head muscle and fin muscle. In the growing fish, RT-PCR results showed that Myf-5 was expressed in the skeletal muscle and intestine. ..
  15. Kablar B, Tajbakhsh S, Rudnicki M. Transdifferentiation of esophageal smooth to skeletal muscle is myogenic bHLH factor-dependent. Development. 2000;127:1627-39 pubmed
    ..Taken together, these results indicate that transdifferentiation is the fate of all smooth muscle cells in the upper esophagus and is normally initiated by Myf5. ..
  16. Daubas P, Crist C, Bajard L, Relaix F, Pecnard E, Rocancourt D, et al. The regulatory mechanisms that underlie inappropriate transcription of the myogenic determination gene Myf5 in the central nervous system. Dev Biol. 2009;327:71-82 pubmed publisher
    ..The Wnt-beta catenin signalling pathway is also implicated. Finally we show that post-transcriptional regulation of Myf5 gene expression involves miRNA repression acting through the Myf5-3'UTR. ..
  17. Ustanina S, Carvajal J, Rigby P, Braun T. The myogenic factor Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification. Stem Cells. 2007;25:2006-16 pubmed
    ..We reason that Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification. Disclosure of potential conflicts of interest is found at the end of this article...
  18. Seo K, Wang Y, Kokubo H, Kettlewell J, Zarkower D, Johnson R. Targeted disruption of the DM domain containing transcription factor Dmrt2 reveals an essential role in somite patterning. Dev Biol. 2006;290:200-10 pubmed
  19. Haldar M, Karan G, Tvrdik P, Capecchi M. Two cell lineages, myf5 and myf5-independent, participate in mouse skeletal myogenesis. Dev Cell. 2008;14:437-45 pubmed publisher
    ..We also demonstrate here the existence of a significant myf5 lineage within ribs that has an important role in rib development, suggested by severe rib defects upon ablating the myf5 lineage. ..
  20. Montarras D, Lindon C, Pinset C, Domeyne P. Cultured myf5 null and myoD null muscle precursor cells display distinct growth defects. Biol Cell. 2000;92:565-72 pubmed
    ..That a null mutation in either gene reduces the proliferative potential of cultured myoblasts raises the possibility that Myf-5 and MyoD serve proliferation of muscle precursor cells. ..
  21. Dechesne C, Wei Q, Eldridge J, Gannoun Zaki L, Millasseau P, Bougueleret L, et al. E-box- and MEF-2-independent muscle-specific expression, positive autoregulation, and cross-activation of the chicken MyoD (CMD1) promoter reveal an indirect regulatory pathway. Mol Cell Biol. 1994;14:5474-86 pubmed
  22. Maak S, Neumann K, Swalve H. Identification and analysis of putative regulatory sequences for the MYF5/MYF6 locus in different vertebrate species. Gene. 2006;379:141-7 pubmed
    ..However, the existence of numerous regulatory elements at large distances to MYF5 and MYF6 points to a very complex pattern of the gene regulation with significant differences between species. ..
  23. Pownall M, Gustafsson M, Emerson C. Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annu Rev Cell Dev Biol. 2002;18:747-83 pubmed
    ..This knowledge will be a foundation for development of stem cell therapies to repair diseased and damaged muscles. ..
  24. Borello U, Berarducci B, Murphy P, Bajard L, Buffa V, Piccolo S, et al. The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis. Development. 2006;133:3723-32 pubmed
    ..Taken together, these results demonstrate that Myf5 is a direct target of Wnt/beta-catenin, and that its full activation requires a cooperative interaction between the canonical Wnt and the Shh/Gli pathways in muscle progenitor cells. ..
  25. Gustafsson M, Pan H, Pinney D, Liu Y, Lewandowski A, Epstein D, et al. Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification. Genes Dev. 2002;16:114-26 pubmed
  26. Lindon C, Albagli O, Domeyne P, Montarras D, Pinset C. Constitutive instability of muscle regulatory factor Myf5 is distinct from its mitosis-specific disappearance, which requires a D-box-like motif overlapping the basic domain. Mol Cell Biol. 2000;20:8923-32 pubmed
    ..Finally, we find that induction of Myf5 perturbs the passage of cells through mitosis, suggesting that regulation of Myf5 levels at mitosis may influence cell cycle progression of Myf5-expressing muscle precursor cells. ..
  27. Smith T, Kachinsky A, Miller J. Somite subdomains, muscle cell origins, and the four muscle regulatory factor proteins. J Cell Biol. 1994;127:95-105 pubmed
    ..The transiently distinct expression patterns of the four MRF proteins identify dorsal and ventral subdomains of somites, and suggest that skeletal muscle cells in somites originate at multiple sites and via multiple molecular pathways. ..
  28. Tajbakhsh S, Rocancourt D, Cossu G, Buckingham M. Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD. Cell. 1997;89:127-38 pubmed
    ..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. ..
  29. Braun T, Bober E, Rudnicki M, Jaenisch R, Arnold H. MyoD expression marks the onset of skeletal myogenesis in Myf-5 mutant mice. Development. 1994;120:3083-92 pubmed
    ..0 wild-type and mutant mice indicating that myogenic factor expression at the level of somites is not a prerequisite for determination and subsequent migration of limb precursor cells. ..
  30. Garry D, Yang Q, Bassel Duby R, Williams R. Persistent expression of MNF identifies myogenic stem cells in postnatal muscles. Dev Biol. 1997;188:280-94 pubmed
    ..These data identify MNF as a marker of quiescent satellite cells and suggest that downstream genes controlled by MNF serve to modulate proliferative growth or differentiation in this unique cell population. ..
  31. Li H, Bourdelas A, Carron C, Gomez C, Boucaut J, Shi D. FGF8, Wnt8 and Myf5 are target genes of Tbx6 during anteroposterior specification in Xenopus embryo. Dev Biol. 2006;290:470-81 pubmed
    ..Our results therefore identify a regulatory cascade governed by Tbx6 in the specification of posterior mesoderm during Xenopus early development. ..
  32. Tajbakhsh S, Buckingham M. Lineage restriction of the myogenic conversion factor myf-5 in the brain. Development. 1995;121:4077-83 pubmed
    ..These observations raise questions about the role of myf-5 in neurogenesis as well as myogenesis, and introduce a new lineage marker for the developing brain. ..
  33. Tajbakhsh S, Bober E, Babinet C, Pournin S, Arnold H, Buckingham M. Gene targeting the myf-5 locus with nlacZ reveals expression of this myogenic factor in mature skeletal muscle fibres as well as early embryonic muscle. Dev Dyn. 1996;206:291-300 pubmed
    ..These results suggest that the myf-5 gene is not activated in only a subset of muscle cells and are consistent with the results on the MyoD knockout mice. ..
  34. Yang J, Mei W, Otto A, Xiao L, Tao Q, Geng X, et al. Repression through a distal TCF-3 binding site restricts Xenopus myf-5 expression in gastrula mesoderm. Mech Dev. 2002;115:79-89 pubmed
    ..The element for ventral mesoderm activation responds to Activin. Together, these results describe a regulatory mosaic of repression and activation, which defines the myf-5 expression profile in the frog gastrula. ..
  35. Neville C, Schmidt M, Schmidt J. Response of myogenic determination factors to cessation and resumption of electrical activity in skeletal muscle: a possible role for myogenin in denervation supersensitivity. Cell Mol Neurobiol. 1992;12:511-27 pubmed
  36. Tallquist M, Weismann K, Hellstrom M, Soriano P. Early myotome specification regulates PDGFA expression and axial skeleton development. Development. 2000;127:5059-70 pubmed
    ..These results underscore the importance of growth factor signaling within the developing somite and suggest an important role for myogenic determination factors in orchestrating normal development of the axial skeleton. ..
  37. Cossu G, Borello U. Wnt signaling and the activation of myogenesis in mammals. EMBO J. 1999;18:6867-72 pubmed
  38. Yablonka Reuveni Z, Rudnicki M, Rivera A, Primig M, Anderson J, Natanson P. The transition from proliferation to differentiation is delayed in satellite cells from mice lacking MyoD. Dev Biol. 1999;210:440-55 pubmed
    ..It is further proposed that the Myf5+/MyoD- phenotype may represent the myogenic stem cell compartment which is capable of maintaining the myogenic precursor pool in the adult muscle. ..
  39. Kassar Duchossoy L, Gayraud Morel B, Gom├Ęs D, Rocancourt D, Buckingham M, Shinin V, et al. Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature. 2004;431:466-71 pubmed
    ..We revise the epistatic relationship of the MRFs, in which both Myf5 and Mrf4 act upstream of Myod to direct embryonic multipotent cells into the myogenic lineage. ..
  40. Groves J, Hammond C, Hughes S. Fgf8 drives myogenic progression of a novel lateral fast muscle fibre population in zebrafish. Development. 2005;132:4211-22 pubmed
    ..We conclude that Fgf8 drives terminal differentiation of a specific population of lateral muscle precursor cells within the early somite...
  41. Yamane A, Amano O, Urushiyama T, Nagata J, Akutsu S, Fukui T, et al. Exogenous hepatocyte growth factor inhibits myoblast differentiation by inducing myf5 expression and suppressing myoD expression in an organ culture system of embryonic mouse tongue. Eur J Oral Sci. 2004;112:177-81 pubmed
    ..This is achieved by controlling the expression of myf5 and myoD mRNAs, thus inhibiting the differentiation of tongue myoblasts. ..
  42. Buonanno A, Apone L, Morasso M, Beers R, Brenner H, Eftimie R. The MyoD family of myogenic factors is regulated by electrical activity: isolation and characterization of a mouse Myf-5 cDNA. Nucleic Acids Res. 1992;20:539-44 pubmed
    ..Using extracellular electrodes to directly stimulate in situ the soleus muscle of rats, we found that 'electrical activity' per se, in absence of the nerve, represses the increases of myogenic factor mRNAs associated with denervation. ..
  43. Chen Y, Tsai H. Treatment with Myf5-morpholino results in somite patterning and brain formation defects in zebrafish. Differentiation. 2002;70:447-56 pubmed
  44. Kablar B, Krastel K, Ying C, Tapscott S, Goldhamer D, Rudnicki M. Myogenic determination occurs independently in somites and limb buds. Dev Biol. 1999;206:219-31 pubmed
    ..Therefore, cells are recruited into the MyoD-dependent myogenic lineage through activation of the -20-kb MyoD enhancer and this occurs independently in somites and limb buds. ..
  45. McKinnell I, Ishibashi J, Le Grand F, Punch V, Addicks G, Greenblatt J, et al. Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex. Nat Cell Biol. 2008;10:77-84 pubmed
    ..Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme. ..
  46. Gensch N, Borchardt T, Schneider A, Riethmacher D, Braun T. Different autonomous myogenic cell populations revealed by ablation of Myf5-expressing cells during mouse embryogenesis. Development. 2008;135:1597-604 pubmed publisher
    ..Individual myogenic cell lineages seem to substitute for each other within the developing embryo. ..
  47. Barth J, Worrell R, Crawford J, Morris J, Ivarie R. Isolation, sequence, and characterization of the bovine myogenic factor-encoding gene myf-5. Gene. 1993;127:185-91 pubmed
    ..The 3' untranslated region contains four AATAAA sites, three of which are used to produce transcripts of 1.5, 2, and 3 kb in bovine fetal muscle RNA. ..
  48. Hopwood N, Pluck A, Gurdon J. Xenopus Myf-5 marks early muscle cells and can activate muscle genes ectopically in early embryos. Development. 1991;111:551-60 pubmed
    ..These results suggest that XMyf5 acts together with XMyoD as one of the set of genes regulating the earliest events of myogenesis, additional factors being required for complete muscle differentiation. ..
  49. Braun T, Arnold H. Myf-5 and myoD genes are activated in distinct mesenchymal stem cells and determine different skeletal muscle cell lineages. EMBO J. 1996;15:310-18 pubmed
    ..Thus skeletal musculature in vertebrates develops from two separate cell lineages and complementation may occur at the cellular level, but not between different myogenic factor genes within one cell. ..
  50. Chang T, Primig M, Hadchouel J, Tajbakhsh S, Rocancourt D, Fernandez A, et al. An enhancer directs differential expression of the linked Mrf4 and Myf5 myogenic regulatory genes in the mouse. Dev Biol. 2004;269:595-608 pubmed
    ..These observations identify A17 as a sequence that targets sites of myogenesis in vivo and raise questions about the mutually exclusive modes of expression and possible promoter/enhancer interactions at the Mrf4-Myf5 locus. ..
  51. Teboul L, Summerbell D, Rigby P. The initial somitic phase of Myf5 expression requires neither Shh signaling nor Gli regulation. Genes Dev. 2003;17:2870-4 pubmed
    ..We suggest that the discrepancy is due to the existence of specific interactions between the enhancer and the Myf5 promoter. ..
  52. Kablar B, Krastel K, Tajbakhsh S, Rudnicki M. Myf5 and MyoD activation define independent myogenic compartments during embryonic development. Dev Biol. 2003;258:307-18 pubmed
    ..Taken together, these data strongly suggest that Myf5 and MyoD regulatory elements respond differentially in different compartments. ..
  53. Lindon C, Montarras D, Pinset C. Cell cycle-regulated expression of the muscle determination factor Myf5 in proliferating myoblasts. J Cell Biol. 1998;140:111-8 pubmed
    ..These results may be significant in view of the possible role of Myf5 in maintaining the determination of proliferating cells and in timing the onset of differentiation. ..