Somitogenesis pp 124-139 | Cite as

bHLH Proteins and Their Role in Somitogenesis

  • Miguel Maroto
  • Tadahiro Iimura
  • J. Kim Dale
  • Yasumasa Bessho
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 638)


The most obvious manifestation of the existence of a segmented, or metameric, body plan in vertebrate embryos is seen during the formation of the somites. Somites are transient embryonic structures formed in a progressive manner from a nonsegmented mesoderm in a highly regulated process called somitogenesis. As development proceeds different compartments are formed within each somite and these progressively follow a variety of differentiation programs to form segmented organs, such as the different bones that make the axial skeleton, body skeletal muscles and part of the dermis. Transcription factors from the basic helix-loop-helix (bHLH) protein family have been described to be implicated in each of the processes involved in somite formation. bHLH proteins are a family of transcription factors characterized by the presence of a DNA binding domain and a dimerization motif that consists of a basic region adjacent to an amphipathic helix, a loop and a second amphipathic helix. In this chapter we will review a number of bHLH proteins known to play a role in somitogenesis.


Notch Signaling bHLH Protein bHLH Transcription Factor Amphipathic Helix Paraxial Mesoderm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gossler A, Hrabe de Angelis M. Somitogenesis. Curr Top Dev Biol 1998; 38:225–287.PubMedCrossRefGoogle Scholar
  2. 2.
    Rawls A, Wilson-Rawls J, Olson EN. Genetic regulation of somite formation. Curr Top Dev Biol 2000; 47:131–154.PubMedCrossRefGoogle Scholar
  3. 3.
    Hirsinger E, Jouve C, Dubrulle J et al. Somite formation and patterning. Int Rev Cytol 2000; 198:1–65.PubMedCrossRefGoogle Scholar
  4. 4.
    Maroto M, Pourquie O. A molecular clock involved in somite segmentation. Curr Top Dev Biol 2001; 51:221–248.PubMedCrossRefGoogle Scholar
  5. 5.
    Catala M, Teillet MA, Le Douarin NM. Organization and development of the tail bud analyzed with the quail-chick chimaera system. Mech Dev 1995; 51:51–65.PubMedCrossRefGoogle Scholar
  6. 6.
    Psychoyos D, Stern CD. Fates and migratory routes of primitive streak cells in the chick embryo. Development 1996; 122:1523–1534.PubMedGoogle Scholar
  7. 7.
    Richardson MK, Allen SP, Wright GM et al. Somite number and vertebrate evolution. Development 1998; 125:151–160.PubMedGoogle Scholar
  8. 8.
    Cooke J, Zeeman EC. A clock and wavefront model for control of the number of repeated structures during animal morphogenesis. J Theor Biol 1976; 58:455–476.PubMedCrossRefGoogle Scholar
  9. 9.
    Meinhardt H. Models of Biological Pattern Formation. London: Academic Press, 1982.Google Scholar
  10. 10.
    Meinhardt H. Models of segmentation. In: Bellairs R, Ede DA, Lash JW, eds. Somites in Developing Embryos. Plenum, New York: NATO ASI Series 1986; 118:179–189.Google Scholar
  11. 11.
    Primmett DR, Norris WE, Carlson GJ et al. Periodic segmental anomalies induced by heat shock in the chick embryo are associated with the cell cycle. Development 1989; 105:119–130.PubMedGoogle Scholar
  12. 12.
    Palmeirim I, Henrique D, Ish-Horowicz D et al. Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis. Cell 1997; 91:639–648.PubMedCrossRefGoogle Scholar
  13. 13.
    Lassar AB, Paterson BM, Weintraub H. Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell 1986; 47:649–656.PubMedCrossRefGoogle Scholar
  14. 14.
    Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 1987; 51:987–1000.PubMedCrossRefGoogle Scholar
  15. 15.
    Massari ME, Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 2000; 20:429–440.PubMedCrossRefGoogle Scholar
  16. 16.
    Ellenberger T, Fass D, Arnaud M et al. Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer. Genes Dev 1994; 8:970–980.PubMedCrossRefGoogle Scholar
  17. 17.
    Ephrussi A, Church GM, Tonegawa S et al. B lineage—specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science 1985; 227:134–140.PubMedCrossRefGoogle Scholar
  18. 18.
    Lassar AB, Buskin JN, Lockshon D et al. MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell 1989; 58:823–831.PubMedCrossRefGoogle Scholar
  19. 19.
    Gossett LA, Kelvin DJ, Sternberg EA et al. A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol 1989; 9:5022–5033.PubMedGoogle Scholar
  20. 20.
    Buskin JN, Hauschka SD. Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. Mol Cell Biol 1989; 9:2627–2640.PubMedGoogle Scholar
  21. 21.
    Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD and myc proteins. Cell 1989; 56:777–783.PubMedCrossRefGoogle Scholar
  22. 22.
    Davis RL, Turner DL. Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning. Oncogene 2001; 20:8342–8357.PubMedCrossRefGoogle Scholar
  23. 23.
    Sasai Y, Kageyama R, Tagawa, Y et al. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev 1992; 6:2620–2634.PubMedCrossRefGoogle Scholar
  24. 24.
    Fisher AL, Ohsako S, Caudy M. The WRPW motif of the hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domain. Mol Cell Biol 1996; 16:2670–2677.PubMedGoogle Scholar
  25. 25.
    Paroush Z, Finley RL, Kidd T et al. Groucho is required for Drosophila neurogenesis, segmentation and sex determination and interacts directly with hairy-related bHLH proteins. Cell 1994;79:805–815.PubMedCrossRefGoogle Scholar
  26. 26.
    Castella P, Sawai S, Nakao K et al. HES-1 repression of differentiation and proliferation in PC12 cells: role for the helix 3-helix 4 domain in transcription repression. Mol Cell Biol 2000; 20:6170–6183.PubMedCrossRefGoogle Scholar
  27. 27.
    Dawson SR, Turner DL, Weintraub H et al. Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression. Mol Cell Biol 1995; 15:6923–6931.PubMedGoogle Scholar
  28. 28.
    Kageyama R, Ishibashi M, Takebayashi K et al. bHLH transcription factors and mammalian neuronal differentiation. Int J Biochem Cell Biol 1997; 29:1389–1399.PubMedCrossRefGoogle Scholar
  29. 29.
    Cooke J. A gene that resuscitates a theory—somitogenesis and a molecular oscillator. Trends Genet 1998; 14:85–88.PubMedCrossRefGoogle Scholar
  30. 30.
    Dale KJ, Pourquie O. A clock-work somite. Bioessays 2000; 22:72–83.PubMedCrossRefGoogle Scholar
  31. 31.
    Jouve C, Palmeirim I, Henrique D et al. Notch signaling is required for cyclic expression of the hairy-like gene HES1 in the presomitic mesoderm. Development 2000; 127:1421–1429.PubMedGoogle Scholar
  32. 32.
    Leimeister C, Dale JK, Fischer A et al. Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through, multiple interacting bHLH factors. Dev Biol 2000; 227:91–103.PubMedCrossRefGoogle Scholar
  33. 33.
    Bessho Y, Sakata R, Komatsu S et al. Dynamic expression and essential functions of Hes7 in somite segmentation. Genes Dev 2001a; 15:2642–2647.PubMedCrossRefGoogle Scholar
  34. 34.
    Dunwoodie SL, Clements M, Sparrow DB et al. Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm. Development 2002; 129:1795–1806.PubMedGoogle Scholar
  35. 35.
    Gajewski M, Sieger D, Alt B et al. Anterior and posterior waves of cyclic her1 gene expression are differentially regulated tn the presomitic mesoderm of zebrafish. Development 2003; 130:4269–4278.PubMedCrossRefGoogle Scholar
  36. 36.
    Holley SA, Geisler R, Nüsslein-Volhard C. Control of her1 expression during zebrafish somitogenesis by a Delta-dependent oscillator and an independent wave-front activity. Genes Dev 2000; 14:1678–1690.PubMedGoogle Scholar
  37. 37.
    Li Y, Fenger U, Niehrs C et al. Cyclic expression of esr9 gene in Xenopus presomitic mesoderm. Differentiation 2003; 71:83–89.PubMedCrossRefGoogle Scholar
  38. 38.
    Oates AC, Ho RK. Hairy/E(spl)-related (Her) genes are central components of the segmentation oscillator and display redundancy with the Delta/Notch signaling pathway in the formation of anterior segmentation boundaries in the zebrafish. Development 2002; 129:2929–2946.PubMedGoogle Scholar
  39. 39.
    Sawada A, Fritz A, Jiang Y et al. Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm and Mesp-b confers the anterior identity to the developing somites. Development 2000; 127:1691–1702.PubMedGoogle Scholar
  40. 40.
    Pasini A, Jiang YJ, Wilkinson DG. Two zebrafish Notch-dependent hairy/Enhancer-of-split-related genes, her6 and her4, are required to maintain the coordination of cyclic gene expression in the presomitic mesoderm. Development 2004; 131:1529–1541.PubMedCrossRefGoogle Scholar
  41. 41.
    Jen WC, Gawantka V, Pollet N et al. Periodic repression of Notch pathway genes governs the segmentation of Xenopus embryos. Genes Dev 1999; 13:1486–1499.PubMedCrossRefGoogle Scholar
  42. 42.
    Bae S, Bessho Y, Hojo M et al. The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation. Development 2000; 127:2933–2943.PubMedGoogle Scholar
  43. 43.
    Koyano-Nakagawa N Kim J Anderson D, Kintner C. Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development 2000; 127:4203–4216.PubMedGoogle Scholar
  44. 44.
    Kawamura A, Koshida S, Hijikata H et al. Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites. Genes Dev 2005; 19:1156–1161PubMedCrossRefGoogle Scholar
  45. 45.
    Barrantes IB, Elia AJ, Wunsch K et al. Interaction between Notch signaling and Lunatic fringe during somite boundary formation in the mouse. Curr Biol. 1999; 9:470–480.PubMedCrossRefGoogle Scholar
  46. 46.
    Sieger D, Tautz D, Gajewski M. The role of Suppressor of Hairless in Notch mediated signaling during zebrafish somitogenesis. Mech Dev 2003; 120:1083–1094.PubMedCrossRefGoogle Scholar
  47. 47.
    Takke C, Campos-Ortega JA. her1, a zebrafish pair-rule like gene, acts downstream of notch signaling to control somite development. Development 1999; 126:3005–3014.PubMedGoogle Scholar
  48. 48.
    Aulehla A, Johnson RL. Dynamic expression of lunatic fringe suggests a link between notch signaling and an autonomous cellular oscillator driving somite segmentation. Dev Biol 1999; 207:49–61.PubMedCrossRefGoogle Scholar
  49. 49.
    Forsberg H, Crozet F, Brown NA. Waves of mouse Lunatic fringe expression, in four-hour eycles at two-hour intervals, precede somite boundary formation. Curr Biol 1998; 8:1027–1030.PubMedCrossRefGoogle Scholar
  50. 50.
    McGrew MJ, Dale JK, Fraboulet S et al. The lunatic fringe gene is a target of the molecular clock linked to somite segmentation in avian embryos. Curr Biol 1998; 8:979–982.PubMedCrossRefGoogle Scholar
  51. 51.
    Bettenhausen B, Hrabe de Angelis M, Simon D et al. Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta. Development 1995; 121:2407–2418.PubMedGoogle Scholar
  52. 52.
    Elmasri H, Liedtke D, Lucking G et al. her7 and hey1, but not lunatic fringe show dynamic expression during somitogenesis in medaka (Oryzias latipes). Gene Expr Patterns 2004; 4:553–559.PubMedCrossRefGoogle Scholar
  53. 53.
    Morimoto M, Takahashi Y, Endo M et al. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity. Nature 2005; 435:354–359.PubMedCrossRefGoogle Scholar
  54. 54.
    Jiang YJ, Aerne BL, Smithers L et al. Notch signaling and the synchronization of the somite segmentation clock. Nature 2000; 408:475–479.PubMedCrossRefGoogle Scholar
  55. 55.
    Horikawa K, Ishimatsu K, Yoshimoto E et al. Noise-resistant and synchronized oscillation of the segmentation clock. Nature 2006; 441:719–723.PubMedCrossRefGoogle Scholar
  56. 56.
    Aulehla A, Wehrle C, Brand-Saberi B et al. Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev Cell 2003; 4:395–406.PubMedCrossRefGoogle Scholar
  57. 57.
    Dale JK, Malapert P, Chal J et al. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dev Cell 2006; 10:355–366.PubMedCrossRefGoogle Scholar
  58. 58.
    Ishikawa A, Kitajima S, Takahashi Y et al. Mouse Nkd1, a Wnt antagonist, exhibits oscillatory gene expression in the PSM under the control of Notch signaling. Mech Dev 2004; 121:1443–1453.PubMedCrossRefGoogle Scholar
  59. 59.
    Henry CA, Urban MK, Dill KK et al. Two linked hairy/Enhancer of split-related zebrafish genes, her1 and her7, function together to refine alternating somite boundaries. Development 2002; 129:3693–3704.PubMedGoogle Scholar
  60. 60.
    Holley SA, Julich D, Rauch GJ et al. her1 and the notch pathway function within the oscillator mechanism that regulates zebrafish somitogenesis. Development 2002; 129:1175–1183.PubMedGoogle Scholar
  61. 61.
    Bessho Y, Miyoshi G, Sakata R et al. Hes:7 a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm. Genes Cells 2001b; 6:175–185.PubMedCrossRefGoogle Scholar
  62. 62.
    Bessho Y, Hirata H, Masamizu Y et al. Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock. Genes Dev 2003; 17:1451–1456.PubMedCrossRefGoogle Scholar
  63. 63.
    Morales AV, Yasuda Y, Ish-Horowicz D. Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling. Dev Cell 2002; 3:63–74.PubMedCrossRefGoogle Scholar
  64. 64.
    Takebayashi K, Sasai Y, Sakai Y et al. Structure, chromosomal locus and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements. J Biol Chem 1994; 269:5150–5156.PubMedGoogle Scholar
  65. 65.
    Strom A, Castella P, Rockwood J et al. Mediation of NGF signaling by posttranslational inhibition of HES-1, a basic helic-loop-helix repressor of neuronal differentiation. Genes Dev 1997; 11:3168–3181.PubMedCrossRefGoogle Scholar
  66. 66.
    Cole SE, Levorse JM, Tilghman SM et al. Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis. Dev Cell 2002; 3:75–84.PubMedCrossRefGoogle Scholar
  67. 67.
    Hirata H, Yoshiura S, Ohtsuka T et al. Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop. Science 2002; 298:840–843.PubMedCrossRefGoogle Scholar
  68. 68.
    Hirata H, Bessho Y, Kokubu H et al. Instability of Hes7 protein is crucial for the somite segmentation clock. Nat Genet 2004; 36:750–754.PubMedCrossRefGoogle Scholar
  69. 69.
    Dale JK, Maroto M. A Hes1-based oscillator in cultured cells and its potential implications for the segmentation clock. Bioessays 2003; 25:200–203.PubMedCrossRefGoogle Scholar
  70. 70.
    Lewis J. Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator. Curr Biol 2003; 13:1398–1408.PubMedCrossRefGoogle Scholar
  71. 71.
    Monk NA. Oscillatory expression of Hes1, p53 and NF-kappaB driven by transcriptional time delays. Curr Biol 2003; 13:1409–1413.PubMedCrossRefGoogle Scholar
  72. 72.
    Dale JK, Maroto M, Dequeant ML et al. Periodic Notch inhibition by Lunatic Fringe underlies the chick segmentation clock. Nature 2003; 421:275–278.PubMedCrossRefGoogle Scholar
  73. 73.
    Joseph EM, Cassetta LA. Mespo: a novel basic helix-loop-helix gene expressed in the presomitic mesoderm and posterior tailbud of Xenopus embryos. Mech Dev 1999; 82:191–194.PubMedCrossRefGoogle Scholar
  74. 74.
    Yoon JK, Moon RT, Wold B. The bHLH class protein pMesogenin1 can specify paraxial mesoderm phenotypes. Dev Biol 2000; 15:376–391.CrossRefGoogle Scholar
  75. 75.
    Buchberger A, Bonneick S, Arnold HH. Expression of the novel basic-helix-loop-helix transcription factor cMespo in presomitic mesoderm of chicken embryos. Mech Dev 2000; 97:223–226.PubMedCrossRefGoogle Scholar
  76. 76.
    Yoo KW, Kim CH, Park HC et al. Characterization and expression of a presomitic mesoderm-specific mespo gene in zebrafish. Dev Genes Evol 2003; 213:203–206.PubMedGoogle Scholar
  77. 77.
    Yoon JK, Wold B. The bHLH regulator pMesogenin1 is required for maturation and segmentation of paraxial mesoderm. Genes Dev 2000; 14:3204–3214.PubMedCrossRefGoogle Scholar
  78. 78.
    Aoyama H, Asamoto K. Determination of somite cells: independence of cell differentiation and morphogenesis. Development 1988; 104:15–28.PubMedGoogle Scholar
  79. 79.
    Bronner-Fraser M, Stern C. Effects of mesodermal tissues on avian neural crest cell migration. Dev Biol 1991; 143:213–217.PubMedCrossRefGoogle Scholar
  80. 80.
    Dubrulle J, McGrew MJ, Pourquie O. FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal hox gene activation. Cell 2001; 106:219–232.PubMedCrossRefGoogle Scholar
  81. 81.
    Palmeirim I, Dubrulle J, Henrique D et al. Uncoupling segmentation and somitogenesis in the chick presomitic mesoderm. Dev Genet 1998; 23:77–85.PubMedCrossRefGoogle Scholar
  82. 82.
    Keynes RJ, Stern CD. Mechanisms of vertebrate segmentation. Development 1988; 103:413–429.PubMedGoogle Scholar
  83. 83.
    Saga Y, Hata N, Kobayashi S et al. Mesp1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation. Development 1996; 122:2769–2778.PubMedGoogle Scholar
  84. 84.
    Saga Y, Hata N, Koseki H et al. Mesp:2 a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. Genes Dev 1997; 11:1827–1839.PubMedCrossRefGoogle Scholar
  85. 85.
    Takahashi T, Inoue T, Gossler A et al. Feedback loops comprising Dll1, Dll3and Mesp2 and differential involvement of Psen1 are essential for rostrocaudal patterning of somites. Development 2003; 130:4259–4268.PubMedCrossRefGoogle Scholar
  86. 86.
    Takahashi Y, Koizumi K, Takagi A et al. Mesp2 initiates somite segmentation through the Notch signaling pathway. Nat Genet 2000; 25:390–396.PubMedCrossRefGoogle Scholar
  87. 87.
    Morimoto M, Takahashi Y, Endo M et al. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity. Nature 2005; 435:354–359.PubMedCrossRefGoogle Scholar
  88. 88.
    Nakajima Y, Morimoto M, Takahashi Y et al. Identification of Epha4 enhancer required for segmental expression and the regulation by Mesp2. Development 2006; 133:2517–2525.PubMedCrossRefGoogle Scholar
  89. 89.
    Saga Y. Genetic rescue of segmentation defect in MesP2-deficient mice by MesP1 gene replacement. Mech Dev 1998; 75:53–66.PubMedCrossRefGoogle Scholar
  90. 90.
    Nomura-Kitabayashi A, Takahashi Y, Kitajima S et al. Hypomorphic Mesp allele distinguishes establishment of rostrocaudal polarity and segment border formation in somitogenesis. Development 2002; 129:2473–2481.PubMedGoogle Scholar
  91. 91.
    Morimoto M, Kiso M, Sasaki N et al. Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis. Dev Biol 2006; 300:687–698.PubMedCrossRefGoogle Scholar
  92. 92.
    Takahashi Y, Kitajima S, Inoue T et al. Differential contributions of Mesp1 and Mesp2 to the epithelialization and rostro-caudal patterning of somites. Development 2005; 132:787–796.PubMedCrossRefGoogle Scholar
  93. 93.
    Yasuhiko Y, Haraguchi S, Kitajima S et al. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression. Proc Natl Acad Sci USA 2006; 103:3651–3656.PubMedCrossRefGoogle Scholar
  94. 94.
    Terasaki H, Murakami R, Yasuhiko Y et al. Transgenic analysis of the medaka mesp-b enhancer in somitogenesis. Dev Growth Differ 2006; 48:153–68.PubMedCrossRefGoogle Scholar
  95. 95.
    Buchberger A, Seidl K, Klein C et al. cMeso1, a novel bHLH transcription factor, is involved in somite formation in chicken embryos. Dev Biol 1998; 199:201–215.PubMedCrossRefGoogle Scholar
  96. 96.
    Buchberger A, Bonneick S, Klein C et al. Dynamic expression of chicken cMeso2 in segmental plate and somites. Dev Dyn 2002; 223:108–118.PubMedCrossRefGoogle Scholar
  97. 97.
    Sparrow DB, Jen WC, Kotecha S et al. Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus embryo and interacts with the Notch pathway. Development 1998; 125:2041–2051PubMedGoogle Scholar
  98. 98.
    Moreno TA, Kintner C. Regulation of segmental patterning by retinoic acid signaling during Xenopus somitogenesis. Dev Cell 2004; 6:205–218.PubMedCrossRefGoogle Scholar
  99. 99.
    Burgess R, Rawls A, Brown D et al. Requirement of the paraxis gene for somite formation and musculoskeletal patterning. Nature 1996; 384:570–573PubMedCrossRefGoogle Scholar
  100. 100.
    Blanar MA, Crossley PH, Peters KG et al. Mesol, a basic-helix-loop-helix protein involved in mammalian presomitic mesoderm development. Proc Natl Acad Sci USA 1995; 20:5870–5874.CrossRefGoogle Scholar
  101. 101.
    Burgess R, Cscrjesi P, Ligon KL et al. Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites. Dev Biol 1995; 168:296–306.PubMedCrossRefGoogle Scholar
  102. 102.
    Quertermous EE, Hidai H, Blanar MA et al. Cloning and characterization of a basic helix-loop-helix protein expressed in early mesoderm and the developing somites. Proc Natl Acad Sci USA 1994; 19:7066–7070.CrossRefGoogle Scholar
  103. 103.
    Sosic D, Brand-Saberi B, Schmidt C et al. Regulation of paraxis expression and somite formation by ectoderm-and neural tube-derived signals. Dev Biol 1997; 185:229–243.PubMedCrossRefGoogle Scholar
  104. 104.
    Shanmugalingam S, Wilson SW. Isolation, expression and regulation of a zebrafish paraxis homologue. Mech Dev 1998; 78:85–89.PubMedCrossRefGoogle Scholar
  105. 105.
    Carpio R, Honoré SM, Araya C et al. Xenopus paraxis homologue shows novel domains of expression. Dev Dyn 2004; 231:609–613.PubMedCrossRefGoogle Scholar
  106. 106.
    Tseng HT, Jamrich M. Identification and developmental expression of Xenopus paraxis. Int J Dev Biol 2004; 48:1155–1158.PubMedCrossRefGoogle Scholar
  107. 107.
    Barnes GL, Alexander PG, Hsu CW et al. Cloning and characterization of chicken Paraxis: a regulator of paraxial mesoderm development and somite formation. Dev Biol 1997; 189:95–111.PubMedCrossRefGoogle Scholar
  108. 108.
    Nakaya Y, Kuroda S, Katagiri YT et al. Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac. I Dev Cell 2004; 7:425–438.CrossRefGoogle Scholar
  109. 109.
    Durbin L, Brennan C, Shiomi K et al. Eph signaling is required for segmentation and differentiation of the somites. Genes Dev 1998; 12:3096–3109.PubMedCrossRefGoogle Scholar
  110. 110.
    Hrabe de Angelis M, McIntyre J, Gossler A. Maintenance of somite borders in mice requires the Delta homologue DIII. Nature 1997; 386:717–721.PubMedCrossRefGoogle Scholar
  111. 111.
    Johnson J, Rhee J, Parsons SM et al. The anterior/posterior polarity of somites is disrupted in paraxis-deficient mice. Dev Biol 2001; 229:176–187.PubMedCrossRefGoogle Scholar
  112. 112.
    Linker C, Lesbros C, Gros J et al. beta-Catenin-dependent Wnt signalling controls the epithelial organisation of somites through the activation of paraxis. Development 2005; 132:3895–905.PubMedCrossRefGoogle Scholar
  113. 113.
    Gros J, Scaal M, Marcelle C. A two-step mechanism for myotome formation in chick, Dev Cell 2004; 6:875–882.PubMedCrossRefGoogle Scholar
  114. 114.
    Kalcheim C, Ben-Yair R. Cell rearrangements during development of the somite and its derivatives, Curr Opin Genet Dev 2005; 15:371–380.PubMedCrossRefGoogle Scholar
  115. 115.
    Ordahl CP, Williams BA, Denetclaw W. Determination and morphogenesis in myogenic progenitor cells: an experimental embryological approach. Curr Top Dev Biol 2000; 48:319–367.PubMedCrossRefGoogle Scholar
  116. 116.
    Hollway G, Currie P. Vertebrate myotome development. Birth Defects Res C Embryo Today 2005; 75:172–179.PubMedCrossRefGoogle Scholar
  117. 117.
    Weinberg ES, Allende ML, Kelly CS et al. Developmental regulation of zebrafish MyoD in wild-type, no tail and spadetail embryos. Development 1996; 122:271–280.PubMedGoogle Scholar
  118. 118.
    Coutelle O, Blagden CS, Hampson R et al. Hedgehog signaling is required for maintenance of myfs and myoD expression and timely terminal differentiation in zebrafish adaxial myogenesis. Dev Biol 2001; 236:136–510.PubMedCrossRefGoogle Scholar
  119. 119.
    Harvey RP. The Xenopus MyoD gene: an unlocalised maternal mRNA predates lineage-restricted expression in the early embryo. Development 1990; 108:669–680.PubMedGoogle Scholar
  120. 120.
    Kato K, Gurdon JB. Single-cell transplantation determines the time when Xenopus muscle precursor cells acquire a capacity for autonomous differentiation. Proc Natl Acad Sci USA 1993; 90:1310–1314.PubMedCrossRefGoogle Scholar
  121. 121.
    Kopan RR, Nye JS, Weintraub H. The intracellular domain of mouse Notch: A constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD. Development 1994; 120:2385–2396.PubMedGoogle Scholar
  122. 122.
    Ott MO, Bober E, Lyons G et al. Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal muscle in the mouse embryo. Development 1991; 111:1097–1107.PubMedGoogle Scholar
  123. 123.
    Sassoon D, Lyons G, Wright WE et al. Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature 1989; 341:303–307.PubMedCrossRefGoogle Scholar
  124. 124.
    Kiefer JC, Hauschka SD. Myf-5 Is Transiently Expressed in Nonmuscle Mesoderm and Exhibits Dynamic Regional Changes within the Presegmented Mesoderm and Somites I–IV. Dev Biol 2001; 232:77–90.PubMedCrossRefGoogle Scholar
  125. 125.
    Lin-Jones J, Hauschka SD. Myogenic determination factor expression in the developing avian limb bud: An RT-PCR analysis. Dev Biol 1996; 174:407–422.PubMedCrossRefGoogle Scholar
  126. 126.
    Tapscott SJ, Davis RL, Thayer MJ et al. MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science 1988; 242:405–141.PubMedCrossRefGoogle Scholar
  127. 127.
    Weintraub H, Tapscott SJ, Davis RL et al. Activation of muscle-specific genes in pigment, nerve, fat, liver and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci USA 1989; 86:5434–5438.PubMedCrossRefGoogle Scholar
  128. 128.
    Rudnicki MA, Braun T, Hinuma S et al. 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; 71:383–390.PubMedCrossRefGoogle Scholar
  129. 129.
    Braun T, Rudnicki MA, Arnold HH et al. Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell 1992; 71:369–382.PubMedCrossRefGoogle Scholar
  130. 130.
    Rudnicki MA, Schnegelsberg PN, Stead RH et al. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 1993; 75:1351–1359.PubMedCrossRefGoogle Scholar
  131. 131.
    Kablar B, Krastel K, Ying C et al. MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle. Development 1997; 124:4729–4738.PubMedGoogle Scholar
  132. 132.
    Kablar B, Asakura A, Krastel K et al. MyoD and Myf-5 define the specification of musculature of distinct embryonic origin. Biochem Cell Biol 1998; 76:1079–1091.PubMedCrossRefGoogle Scholar
  133. 133.
    Kablar B, Krastel K, Tajbakhsh S et al. Myf5 and MyoD activation define independent myogenic compartments during embryonic development. Dev Biol 2003; 258:307–318.PubMedCrossRefGoogle Scholar
  134. 134.
    Carvajal JJ, Cox D, Summerbell D et al. A BAC transgenic analysis of the Mrf4/Myf5 locus reveals interdigitated elements that control activation and maintenance of gene expression during muscle development. Development 2001; 128:1857–1868.PubMedGoogle Scholar
  135. 135.
    Gustafsson MK, Pan H, Pinney DF et al. Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification. Genes Dev 2002; 16:114–126.PubMedCrossRefGoogle Scholar
  136. 136.
    Hadchouel J, Tajbakhsh S, Primig M et al. Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo. Development 2000; 127:4455–4467.PubMedGoogle Scholar
  137. 137.
    Summerbell D, Ashby PR, Coutelle O et al. The expression of Myf5 in the developing mouse embryo is controlled by discrete and dispersed enhancers specific for particular populations of skeletal muscle precursors. Development 2000; 127:3745–3757.PubMedGoogle Scholar
  138. 138.
    Teboul L, Hadchouel J, Daubas P et al. The early epaxial enhancer is essential for the initial expression of the skeletal muscle determination gene Myf5 but not for subsequent, multiple phases of somitic myogenesis. Development 2002; 129:4571–4580.PubMedGoogle Scholar
  139. 139.
    Munsterberg AE, Kitajewski J, Bumcrot DA et al. Combinatorial signaling by Sonic hedgehog and Wnt family members induces myogenic bHLH gene expression in the somite. Genes Dev 1995; 9:2911–2922.PubMedCrossRefGoogle Scholar
  140. 140.
    Maroto M, Reshef R, Munsterberg AE et al. Ectopic Pax-3 activates MyoD and Myf-5 expression in embryonic mesoderm and neural tissue. Cell 1997; 89:139–148.PubMedCrossRefGoogle Scholar
  141. 141.
    Reshef R, Maroto M, Lassar AB. Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression. Genes Dev 1998; 12:290–303.PubMedCrossRefGoogle Scholar
  142. 142.
    Tajbakhsh S, Borello U, Vivarelli E 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; 125:4155–4162.PubMedGoogle Scholar
  143. 143.
    Olson EN. Proto-oncogenes in the regulatory circuit for myogenesis. Semin Cell Biol 1992; 3:127–136.PubMedCrossRefGoogle Scholar
  144. 144.
    Li L, Zhou J, James G et al. FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains. Cell 1992; 71:1181–1194.PubMedCrossRefGoogle Scholar
  145. 145.
    Bengal E, Ransone L, Scharfmann R et al. Functional antagonism between c-Jun and MyoD proteins: a direct physical association. Cell 1992; 68:507–519.PubMedCrossRefGoogle Scholar
  146. 146.
    Benezra R, Davis RL, Lockshon D et al. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 1990; 61:49–59.PubMedCrossRefGoogle Scholar
  147. 147.
    Ruzinova MB, Benezra R. Id proteins in development, cell cycle and cancer. Trends Cell Biol 2003; 13:410–418.PubMedCrossRefGoogle Scholar
  148. 148.
    Fuchbauer EM. Expression of M-twist during postimplantation development of the mouse. Dev Dyn 1995; 204:316–322.Google Scholar
  149. 149.
    Spicer DB, Rhee J, Cheung WL et al. Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein Twist. Science 1996; 272:1476–1480.PubMedCrossRefGoogle Scholar
  150. 150.
    Stoetzel C, Weber B, Bourgeois P et al. Dorso-ventral and rostro-caudal sequential expression of M-twist in the postimplantation murine embryo. Mech Dev 1995; 51:251–263.PubMedCrossRefGoogle Scholar
  151. 151.
    Hamamori Y, Wu HY, Sartorelli V et al. 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; 17:6563–6573.PubMedGoogle Scholar
  152. 152.
    Chen ZF, Behringer RR. Twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev 1995; 9:686–699.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Miguel Maroto
    • 1
  • Tadahiro Iimura
    • 2
  • J. Kim Dale
    • 1
  • Yasumasa Bessho
    • 3
  1. 1.College of Life SciencesUniversity of DundeeDundeeScotland, UK
  2. 2.Stowers Institute for Medical ResearchKansas CityUSA
  3. 3.Graduate School of Biological SciencesNara Institute of Science and TechnologyTakayama, IkomaJapan

Personalised recommendations