Gene Symbol: Myf6
Description: myogenic factor 6
Alias: MRF4, bHLHc4, herculin, myogenic factor 6, muscle-specific regulatory factor 4, myf-6
Species: mouse
Products:     Myf6

Top Publications

  1. Hannon K, Smith C, Bales K, Santerre R. Temporal and quantitative analysis of myogenic regulatory and growth factor gene expression in the developing mouse embryo. Dev Biol. 1992;151:137-44 pubmed
    ..chain reaction method, the temporal pattern of expression of the myogenic regulatory genes (myf5, myogenin, MRF4, myo D) was quantitated in developing mouse muscle (whole embryo: 6.5 to 12...
  2. Li G, Kikuchi K, Radka M, Abraham J, Rubin B, Keller C. IL-4 receptor blockade abrogates satellite cell: rhabdomyosarcoma fusion and prevents tumor establishment. Stem Cells. 2013;31:2304-12 pubmed publisher
    ..Taken together, this study supports a potential role of tumor cell-host cell fusion and the strong therapeutic potential of IL-4R blockade to prevent the establishment of RMS tumors at new anatomical sites. ..
  3. Weintraub H, Davis R, Tapscott S, Thayer M, Krause M, Benezra R, et al. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991;251:761-6 pubmed
    ..MyoD is expressed only in skeletal muscle and its precursors; in nonmuscle cells myoD is repressed by specific genes. MyoD activates its own transcription; this may stabilize commitment to myogenesis. ..
  4. Bober E, Lyons G, Braun T, Cossu G, Buckingham M, Arnold H. The muscle regulatory gene, Myf-6, has a biphasic pattern of expression during early mouse development. J Cell Biol. 1991;113:1255-65 pubmed
    The spatial and temporal expression pattern of the muscle regulatory gene Myf-6 (MRF4/herculin) has been investigated by in situ hybridization during embryonic and fetal mouse development...
  5. Nishijo K, Chen Q, Zhang L, McCleish A, Rodriguez A, Cho M, et al. Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma. Cancer Res. 2009;69:2902-11 pubmed publisher
    ..We further identified 7 "druggable" kinases overexpressed across species. The data affirm the accuracy of this genetically engineered mouse model...
  6. Zhang W, Behringer R, Olson E. Inactivation of the myogenic bHLH gene MRF4 results in up-regulation of myogenin and rib anomalies. Genes Dev. 1995;9:1388-99 pubmed
    The myogenic basic helix-loop-helix (bHLH) proteins MyoD, myf5, myogenin, and MRF4 can initiate myogenesis when expressed in nonmuscle cells...
  7. Kassar Duchossoy L, Giacone E, Gayraud Morel B, Jory A, Gomès D, Tajbakhsh S. Pax3/Pax7 mark a novel population of primitive myogenic cells during development. Genes Dev. 2005;19:1426-31 pubmed
    ..These findings identify critical cell populations during lineage restriction, and provide a framework for defining myogenic cell states for therapeutic studies. ..
  8. Braun T, Rudnicki M, Arnold H, Jaenisch R. Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell. 1992;71:369-82 pubmed
  9. Abraham J, Chua Y, Glover J, Tyner J, Loriaux M, Kilcoyne A, et al. An adaptive Src-PDGFRA-Raf axis in rhabdomyosarcoma. Biochem Biophys Res Commun. 2012;426:363-8 pubmed publisher
    ..These results suggest that an adaptive Src-Pdgfra-Raf-Mapk axis is relevant to PDGFRA inhibition in rhabdomyosarcoma. ..

Scientific Experts

More Information


  1. Patapoutian A, Yoon J, Miner J, Wang S, Stark K, Wold B. Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome. Development. 1995;121:3347-58 pubmed
    MRF4 (herculin/Myf-6) is one of the four member MyoD family of transcription factors identified by their ability to enforce skeletal muscle differentiation upon a wide variety of nonmuscle cell types...
  2. Haldar M, Hancock J, Coffin C, Lessnick S, Capecchi M. A conditional mouse model of synovial sarcoma: insights into a myogenic origin. Cancer Cell. 2007;11:375-88 pubmed
    ..We also show that early widespread expression of the fusion protein disrupts normal embryogenesis, causing lethality. ..
  3. Keller C, Arenkiel B, Coffin C, El Bardeesy N, Depinho R, Capecchi M. Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function. Genes Dev. 2004;18:2614-26 pubmed
    ..knock-in allele whose activation in late embryogenesis and postnatally is targeted to terminally differentiating Myf6-expressing skeletal muscle...
  4. Sabourin L, Rudnicki M. The molecular regulation of myogenesis. Clin Genet. 2000;57:16-25 pubmed
    ..have unraveled important mechanisms by which the four myogenic regulatory factors (MRFs: MyoD, Myf-5, myogenin, and MRF4) control the specification and the differentiation of the muscle lineage...
  5. Michalak S, Whitman M, Park J, Tischfield M, Nguyen E, Engle E. Ocular Motor Nerve Development in the Presence and Absence of Extraocular Muscle. Invest Ophthalmol Vis Sci. 2017;58:2388-2396 pubmed publisher
    ..These data suggest that intermediate targets in the mesenchyme provide cues necessary for appropriate targeting of ocular motor axons to the orbit, while EOM cues are responsible for terminal branching and motor neuron survival. ..
  6. Vinagre T, Moncaut N, Carapuco M, Novoa A, Bom J, Mallo M. Evidence for a myotomal Hox/Myf cascade governing nonautonomous control of rib specification within global vertebral domains. Dev Cell. 2010;18:655-61 pubmed publisher
    ..and rib-less areas is first interpreted in the myotome through the regional-specific control of Myf5 and Myf6 expression...
  7. Washabaugh C, Ontell M, Shand S, Bradbury N, Kant J, Ontell M. Neuronal control of myogenic regulatory factor accumulation in fetal muscle. Dev Dyn. 2007;236:732-45 pubmed
    ..g., myoD and myogenin [E16.5-E18.5] and MRF4 in the EDL only [E18.5-E19...
  8. 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
    ..To examine MRF function and regulation in somites, we generated myogenin promoter-MRF4 transgenic mice in which MRF4 was expressed in rostral somites about a half day earlier than normal...
  9. Smith T, Block N, Rhodes S, Konieczny S, Miller J. A unique pattern of expression of the four muscle regulatory factor proteins distinguishes somitic from embryonic, fetal and newborn mouse myogenic cells. Development. 1993;117:1125-33 pubmed
    ..Expression of the myosin heavy chain (MHC), MyoD, myogenin, Myf-5, and MRF4 proteins was examined by immunocytochemistry in cultures of four distinct types of mouse myogenic cells: somitic (..
  10. Fundele R, Bober E, Arnold H, Grim M, Bender R, Wilting J, et al. Early skeletal muscle development proceeds normally in parthenogenetic mouse embryos. Dev Biol. 1994;161:30-6 pubmed
    ..The underrepresentation in older chimeras may therefore be due to selective elimination. These data also argue against imprinting of the myogenic factor genes myogenin, Myf-5, and Myf-6. ..
  11. Haines B, Gupta R, Jones C, Summerbell D, Rigby P. The NLRR gene family and mouse development: Modified differential display PCR identifies NLRR-1 as a gene expressed in early somitic myoblasts. Dev Biol. 2005;281:145-59 pubmed
    ..The regulated embryonic expression and cellular location of these proteins suggest important roles during mouse development in the control of cell adhesion, movement or signalling. ..
  12. Sabourin L, Girgis Gabardo A, Seale P, Asakura A, Rudnicki M. Reduced differentiation potential of primary MyoD-/- myogenic cells derived from adult skeletal muscle. J Cell Biol. 1999;144:631-43 pubmed
    ..Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally...
  13. Sambasivan R, Comai G, Le Roux I, Gomès D, Konge J, Dumas G, et al. Embryonic founders of adult muscle stem cells are primed by the determination gene Mrf4. Dev Biol. 2013;381:241-55 pubmed publisher
    ..Selective induction of the muscle determination genes Myf5, Myod and Mrf4 during prenatal development can potentially impact on the reported functional heterogeneity of adult satellite ..
  14. Arnold H, Braun T. Genetics of muscle determination and development. Curr Top Dev Biol. 2000;48:129-64 pubmed
    ..Finally, we present recent evidence on genes that play a role in regeneration of muscle in adult organisms. ..
  15. Borensztein M, Viengchareun S, Montarras D, Journot L, Binart N, Lombes M, et al. Double Myod and Igf2 inactivation promotes brown adipose tissue development by increasing Prdm16 expression. FASEB J. 2012;26:4584-91 pubmed publisher
  16. 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. ..
  17. Roth J, Shikama N, Henzen C, Desbaillets I, Lutz W, Marino S, et al. Differential role of p300 and CBP acetyltransferase during myogenesis: p300 acts upstream of MyoD and Myf5. EMBO J. 2003;22:5186-96 pubmed
    ..These data reveal a specific requirement for p300 and its AT activity in the induction of MRF gene expression and myogenic cell fate determination in vivo. ..
  18. Carvajal J, Keith A, Rigby P. Global transcriptional regulation of the locus encoding the skeletal muscle determination genes Mrf4 and Myf5. Genes Dev. 2008;22:265-76 pubmed publisher
    The linked Mrf4 and Myf5 genes encode two transcription factors essential for the determination and differentiation of skeletal muscle in the embryo...
  19. Rawls A, Morris J, Rudnicki M, Braun T, Arnold H, Klein W, et al. Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis. Dev Biol. 1995;172:37-50 pubmed
    The four myogenic basic helix-loop-helix proteins, MyoD, myogenin, Myf-5, and MRF4, can each activate skeletal muscle differentiation when introduced into nonmuscle cells...
  20. Yamane A, Ohnuki Y, Saeki Y. Delayed embryonic development of mouse masseter muscle correlates with delayed MyoD family expression. J Dent Res. 2000;79:1933-6 pubmed
    ..The expression of MRF4 mRNA began later in the masseter (E15) than in the tongue (E13)...
  21. Miner J, Wold B. Herculin, a fourth member of the MyoD family of myogenic regulatory genes. Proc Natl Acad Sci U S A. 1990;87:1089-93 pubmed
    We have identified and cloned herculin, a fourth mouse muscle regulatory gene...
  22. Wang Q, Hebert S, Rich M, Kraner S. Loss of synaptic vesicles from neuromuscular junctions in aged MRF4-null mice. Neuroreport. 2011;22:185-9 pubmed publisher
    b>MRF4 belongs to the basic helix-loop-helix class of transcription factors and this and other members of its family profoundly influence skeletal muscle development. Less is known about the role of these factors in aging...
  23. Nagandla H, Lopez S, Yu W, Rasmussen T, Tucker H, Schwartz R, et al. Defective myogenesis in the absence of the muscle-specific lysine methyltransferase SMYD1. Dev Biol. 2016;410:86-97 pubmed publisher
    ..Thus, in addition to the previously described functions for Smyd1 in heart development and skeletal muscle sarcomerogenesis, these results point to a novel role for Smyd1 in myoblast differentiation. ..
  24. Olson E, Edmondson D, Wright W, Lin V, Guenet J, Simon Chazottes D, et al. Myogenin is in an evolutionarily conserved linkage group on human chromosome 1q31-q41 and unlinked to other mapped muscle regulatory factor genes. Genomics. 1990;8:427-34 pubmed
    ..of a family of muscle-specific regulatory factors which includes MyoD1, Myf-5, and Myf-6 (also called MRF4 and herculin)...
  25. 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
    ..In trunk somites, however, MyoD is initially expressed in ventral cells. Myogenin and MRF4 are restricted to myotome cells, though the MRF4-expressing cells are initially less widely distributed than the ..
  26. Gayraud Morel B, Chretien F, Flamant P, Gomès D, Zammit P, Tajbakhsh S. A role for the myogenic determination gene Myf5 in adult regenerative myogenesis. Dev Biol. 2007;312:13-28 pubmed
    The myogenic determination genes Myf5, Myod and Mrf4 direct skeletal muscle cell fate prenatally...
  27. Yamane A, Mayo M, Shuler C, Crowe D, Ohnuki Y, Dalrymple K, et al. Expression of myogenic regulatory factors during the development of mouse tongue striated muscle. Arch Oral Biol. 2000;45:71-8 pubmed
    ..Expression of MRF4 mRNA appeared earlier in the tongue (E13) than in the hind-limb muscle (E15) and increased in both muscles after ..
  28. Hasty P, Bradley A, Morris J, Edmondson D, Venuti J, Olson E, et al. Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature. 1993;364:501-6 pubmed
    ..Myogenin-mutant mice differ from mice carrying mutations in genes for the related myogenic factors Myf5 and MyoD, which have no muscle defects. Myogenin is therefore essential for the development of functional skeletal muscle. ..
  29. Evans S, Tai L, Tan V, Newton C, Chien K. Heterokaryons of cardiac myocytes and fibroblasts reveal the lack of dominance of the cardiac muscle phenotype. Mol Cell Biol. 1994;14:4269-79 pubmed
  30. Tanner C, Madsen S, Hallowell D, Goring D, Moore T, Hardman S, et al. Mitochondrial and performance adaptations to exercise training in mice lacking skeletal muscle LKB1. Am J Physiol Endocrinol Metab. 2013;305:E1018-29 pubmed publisher
    ..Our findings indicate that skeletal muscle LKB1 is required for accretion of some mitochondrial proteins but not for early exercise capacity improvements with exercise training. ..
  31. Hinterberger T, Sassoon D, Rhodes S, Konieczny S. Expression of the muscle regulatory factor MRF4 during somite and skeletal myofiber development. Dev Biol. 1991;147:144-56 pubmed
    The muscle regulatory factors MRF4, myogenin, myf-5, and MyoD constitute a family of proteins that can function as muscle-specific transcriptional activators...
  32. Comai G, Sambasivan R, Gopalakrishnan S, Tajbakhsh S. Variations in the efficiency of lineage marking and ablation confound distinctions between myogenic cell populations. Dev Cell. 2014;31:654-67 pubmed publisher
    The myogenic regulatory genes Myf5, Mrf4, Myod, and Myogenin likely arose by gene duplications during evolution, presumably to address the more demanding requirements of the vertebrate body plan...
  33. Abraham J, Núñez Álvarez Y, Hettmer S, Carrió E, Chen H, Nishijo K, et al. Lineage of origin in rhabdomyosarcoma informs pharmacological response. Genes Dev. 2014;28:1578-91 pubmed publisher
  34. Bureau J, Bihl F, Brahic M, Le Paslier D. The gene coding for interferon-gamma is linked to the D12S335 and D12S313 microsatellites and to the MDM2 gene. Genomics. 1995;28:109-12 pubmed
    ..Finally, we describe the organization of the Ifg, Myf-6, Mdm1, and Mdm2 loci on mouse chromosome 10, in a region syntenic to human chromosome band 12q15. ..
  35. Thompson A, Filatov G, Chen C, Porter I, Li Y, Rich M, et al. A selective role for MRF4 in innervated adult skeletal muscle: Na(V) 1.4 Na+ channel expression is reduced in MRF4-null mice. Gene Expr. 2005;12:289-303 pubmed
    ..4, are poorly understood. Here we tested the role of the transcription factor MRF4, one of four basic helix-loop-helix (bHLH) factors expressed in skeletal muscle, in regulation of the Na(V) 1...
  36. Valdez M, Richardson J, Klein W, Olson E. Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4. Dev Biol. 2000;219:287-98 pubmed
    The basic helix-loop-helix (bHLH) transcription factors-MyoD, Myf5, myogenin, and MRF4-can each activate the skeletal muscle-differentiation program in transfection assays...
  37. Hamamori Y, Wu H, Sartorelli V, Kedes L. The basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist. Mol Cell Biol. 1997;17:6563-73 pubmed
    ..These findings demonstrate that M-Twist interacts with MyoD through the basic domains, thereby inhibiting MyoD. ..
  38. Laurent A, Pinset C, Aurade F, Vidaud M, Montarras D. Expression of myotonic dystrophy protein kinase gene during in vivo and in vitro mouse myogenesis. Cell Mol Biol (Noisy-le-grand). 1997;43:881-8 pubmed
    ..Results show that DMPK gene expression is upregulated at a late stage of muscular development. This upregulation does not seem to depend on a given muscle specific bHLH factor. ..
  39. Moga M, Nakamura T, Robbins J. Genetic approaches for changing the heart and dissecting complex syndromes. J Mol Cell Cardiol. 2008;45:148-55 pubmed publisher
    ..Increasingly precise and modifiable animal models of human cardiac disease will allow researchers to determine not only pathogenesis, but also guide treatment and the development of novel therapies. ..
  40. Grifone R, Demignon J, Houbron C, Souil E, Niro C, Seller M, et al. Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo. Development. 2005;132:2235-49 pubmed
    ..myotome, absence of Six1 and Six4 impairs the expression of the myogenic regulatory factors myogenin and Myod1, and Mrf4 expression becomes undetectable...
  41. Jin X, Kim J, Oh M, Oh H, Sohn Y, Pian X, et al. Opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation. Biochem Biophys Res Commun. 2007;364:476-82 pubmed
    ..Among the myogenic regulatory factors (MRFs), MRF4 shows a biphasic expression pattern during the formation of myotomes, although its function remains unclear...
  42. Rubin B, Nishijo K, Chen H, Yi X, Schuetze D, Pal R, et al. Evidence for an unanticipated relationship between undifferentiated pleomorphic sarcoma and embryonal rhabdomyosarcoma. Cancer Cell. 2011;19:177-91 pubmed publisher
    ..Thus, sarcoma phenotype is strongly influenced by cell of origin and mutational profile. ..
  43. Yoon J, Moon R, Wold B. The bHLH class protein pMesogenin1 can specify paraxial mesoderm phenotypes. Dev Biol. 2000;222:376-91 pubmed
  44. Southard S, Low S, Li L, Rozo M, Harvey T, Fan C, et al. A series of Cre-ER(T2) drivers for manipulation of the skeletal muscle lineage. Genesis. 2014;52:759-70 pubmed publisher
    ..tamoxifen-inducible Cre (Cre-ER(T) (2) ; CE) gene cassette knocked into the endogenous loci of Pax3, Myod1, Myog, Myf6, and Myl1, collectively as a resource for the skeletal muscle research community...
  45. Floss T, Arnold H, Braun T. Myf-5(m1)/Myf-6(m1) compound heterozygous mouse mutants down-regulate Myf-5 expression and exert rib defects: evidence for long-range cis effects on Myf-5 transcription. Dev Biol. 1996;174:140-7 pubmed
    ..These results indicate that the Myf-6 mutation inhibits Myf-5 gene expression by a long-range cis effect. ..
  46. Yoon J, Olson E, Arnold H, Wold B. Different MRF4 knockout alleles differentially disrupt Myf-5 expression: cis-regulatory interactions at the MRF4/Myf-5 locus. Dev Biol. 1997;188:349-62 pubmed
    Three different null alleles of the myogenic bHLH gene MRF4/herculin/Myf-6 were created recently...
  47. Ma Z, Sun X, Xu D, Xiong Y, Zuo B. MicroRNA, miR-374b, directly targets Myf6 and negatively regulates C2C12 myoblasts differentiation. Biochem Biophys Res Commun. 2015;467:670-5 pubmed publisher
    ..differentiation and myotube formation and is controlled by myogenic regulatory factors (MRFs), MyoD, MyoG, Myf5 and Myf6 (also known as MRF4)...
  48. Summerbell D, Halai C, Rigby P. Expression of the myogenic regulatory factor Mrf4 precedes or is contemporaneous with that of Myf5 in the somitic bud. Mech Dev. 2002;117:331-5 pubmed
    ..In the somites of the mouse embryo the order of expression is thought to be Myf5, Myogenin, Mrf4 and MyoD...
  49. Kikuchi K, Hettmer S, Aslam M, Michalek J, Laub W, Wilky B, et al. Cell-cycle dependent expression of a translocation-mediated fusion oncogene mediates checkpoint adaptation in rhabdomyosarcoma. PLoS Genet. 2014;10:e1004107 pubmed publisher
    ..Thus, the surprisingly dynamic regulation of the Pax3:Foxo1a locus is a paradigm that has important implications for the way in which oncogenes are modeled in cancer cells. ..
  50. Yamane A, Takahashi K, Mayo M, Vo H, Shum L, Zeichner David M, et al. Induced expression of myoD, myogenin and desmin during myoblast differentiation in embryonic mouse tongue development. Arch Oral Biol. 1998;43:407-16 pubmed
    ..mouse tongue through the induction of myogenic regulatory factors such as myoD, myf5, myogenin and MRF4/myf6/herculin. To test this hypothesis, the effects of exogenous TGF alpha on the transcription of myoD, myf5, myogenin, MRF4 ..
  51. Block N, Miller J. Expression of MRF4, a myogenic helix-loop-helix protein, produces multiple changes in the myogenic program of BC3H-1 cells. Mol Cell Biol. 1992;12:2484-92 pubmed
    Expression of MRF4, a myogenic regulatory factor of the basic helix-loop-helix type, produced multiple changes in the myogenic program of the BC3H-1 cell line...
  52. Vivian J, Gan L, Olson E, Klein W. A hypomorphic myogenin allele reveals distinct myogenin expression levels required for viability, skeletal muscle development, and sternum formation. Dev Biol. 1999;208:44-55 pubmed
  53. Innocenzi A, Latella L, Messina G, Simonatto M, Marullo F, Berghella L, et al. An evolutionarily acquired genotoxic response discriminates MyoD from Myf5, and differentially regulates hypaxial and epaxial myogenesis. EMBO Rep. 2011;12:164-71 pubmed publisher