Journal of Muscle Research & Cell Motility

, Volume 23, Issue 3, pp 255–264 | Cite as

Six and Eya expression during human somitogenesis and MyoD gene family activation

  • Françoise Fougerousse
  • Muriel Durand
  • Soledad Lopez
  • Laurence Suel
  • Josiane Demignon
  • Charles Thornton
  • Hidenori Ozaki
  • Kyoshi Kawakami
  • Patrick Barbet
  • Jacques S. Beckmann
  • Pascal Maire
Article

Abstract

This report describes the characterisation of the expression profile of several myogenic determination genes during human embryogenesis. The data were obtained from axial structures and limb buds of human embryos aged between 3 and 8 weeks of development. Using in situ hybridisation to detect Pax3 and MyoD gene family mRNAs, and immunochemistry to follow Six and Eya protein accumulation, we have been able to establish the chronology of accumulation of these gene products. As in mouse, the first transcripts detected in myotomes of 3 week-old embryos are Pax3 and Myf5, followed by the expression of myogenin. MyoD appears to be activated well after Myf5, myogenin and MRF4 in the early myotome, whereas, in limb bud muscles, the presence of all four of these mRNAs is concomitant from 6 weeks. Six1, Six4 and Six5 homeoproteins are detected later than Myf5 activation. These Six homeoproteins are first observed in the cytoplasm of myogenin expressing cells. At later stages of development, Six1 and Six5, but not Six4, are translocated into the nuclei of myogenic cells, concomitantly with MyHCemb expression. Eya1 and Eya2 proteins, potential Six cofactors, were also detected in myogenin positive cells, but their accumulation was delayed and was mainly cytoplasmic. These results preclude that early activation of Myf5, myogenin and MRF4 is under the control of Six and Eya proteins, while Six and Eya proteins would be involved in later steps of myogenic differentiation.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, Levi-Acobas F, Cruaud C, Le Merrer M, Mathieu M, Konig R, Vigneron J, Weissenbach J, Petit C and Weil D (1997) Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1. Hum Mol Genet 6: 2247-2255.Google Scholar
  2. Bonini N, Leiserson W and Benzer S (1998) Multiple roles of the eyes absent gene in Drosophila. Dev Biol 196: 42-57.Google Scholar
  3. Borsani G, DeGrandi A, Ballabio A, Bulfone ABL, Banfi S, Gattuso C, Mariani M, Dixon M, Donnai D, Metcalfe K, Winter R, Robertson M, Axton R, Brown A, van Heyningen V and Hanson IM (1999) EYA4, a novel vertebrate gene related to Drosophila eyes absent. Hum Mol Genet 8: 11-23.Google Scholar
  4. Boyle M, Bonini N and DiNardo S (1997) Expression and function of clift in the development of somatic gonadal precursors within the Drosophila mesoderm. Development 124: 971-982.Google Scholar
  5. Buckingham M (1992) Making muscle in mammals. Trends Genet 8: 144-148.Google Scholar
  6. Buckingham M (2001) Skeletal muscle formation in vertebrates. Curr Opin Genet Dev 11: 440-448.Google Scholar
  7. Cheyette B, Green P, Martin K, Garren H, Hartenstein V and Zipursky S (1994) The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron 12: 977-996.Google Scholar
  8. Cusella-De Angelis M, Lyons G, Sonnino C, De Angelis L, Vivarelli E, Farmer K, Wright W, Molinaro M, Bouche M, Buckingham M and Cossu G (1992) MyoD, myogenin independent differentiation of primordial myoblasts in mouse somites. J Cell Biol 116: 1243-1255.Google Scholar
  9. Damiani E, Angelini C, Pelosi M, Sacchetto R, Bortoloso E and Margreth A (1996) Skeletal muscle sarcoplasmic reticulum phenotype in myotonic dystrophy. Neuromuscul Disord 6: 33-47.Google Scholar
  10. Edom-Vovard F, Mouly V, Barbet JP and Butler-Browne G (1999) The four populations of myoblasts involved in human limb muscle formation are present from the onset of primary myotube formation. J Cell Sci 112: 191-199.Google Scholar
  11. Fan X, Brass L, Poncz M, Spitz F, Maire P and Manning D (2000) The α subunit of Gz and Gi interact with the eyes absent transcription cofactor Eya2, preventing its interaction with the six class of homeodomain-containing proteins. J Biol Chem 275: 32,129-32,134.Google Scholar
  12. Farkas-Bargeton E, Barbet JP, Dancea S, Wehrle R, Checouri A and Dulac O (1988) Immaturity of muscle fibers in the congenital form of myotonic dystrophy: its consequences and its origin. J Neurol Sci 83: 145-159.Google Scholar
  13. Fougerousse F, Anderson LV, Delezoide AL, Suel L, Durand M and Beckmann JS (2000) Calpain3 expression during human cardiogenesis. Neuromuscul Disord 10: 251-256.Google Scholar
  14. Fougerousse F, Durand M, Suel L, Pourquie O, Delezoide AL, Romero N, Abitbol M and Beckmann JS (1998) Expression of genes (CAPN3, SGCA, SGCB, and TTN) involved in progressive muscular dystrophies during early human development. Genomics 48: 145-156.Google Scholar
  15. Gallardo M, Lopez-Rios J, Fernaud-Espinosa I, Granadino B, Sanz R, Ramos C, Ayuso C, Seller M, Brunner H, Bovolenta P and Rodriguez de Cordoba S (1999) Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies. Genomics 61: 82-91.Google Scholar
  16. Gerard M, Abitbol M, Delezoide AL, Dufier J, Mallet J and Vekemans M (1995) PAX-genes expression during human embryonic development, a preliminary report. C R Acad Sci III 318: 57-66.Google Scholar
  17. Gonzalez-Crespo S, Abu-Shaar M, Torres M, Martinez-AC, Mann R and Morata G (1998) Antagonism between extradenticle function and Hedgehog signalling in the developing limb. Nature 394: 196-200.Google Scholar
  18. Halder G, Callaerts P, Flister S, Walldorf U, Kloter U and Gehring W (1998) Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development 125: 2181-2191.Google Scholar
  19. Heanue T, Reshef R, Davis R, Mardon G, Oliver G, Tomarev S, Lassar A and Tabin C (1999) Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. Genes Dev 13: 3231-3243.Google Scholar
  20. Hoth C, Milunsky A, Lipsky N, Sheffer R, Clarren S and Baldwin C (1993) Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). Am J Hum Genet 63: 29-32.Google Scholar
  21. Iannaccone S, Bove K, Vogler C, Azzarelli B and Muller J (1986) Muscle maturation delay in infantile myotonic dystrophy. Arch Pathol Lab Med 110: 405-411.Google Scholar
  22. Kawakami K, Ohto H, Ikeda K and Roeder R (1996) Structure, function and expression of a murine homeobox protein AREC3, a homologue of Drosophila sine oculis gene product, and implication in development. Nucleic Acids Res 24: 303-310.Google Scholar
  23. Kawakami K, Sato S, Ozaki H and Ikeda K (2000) Six family genes-structure and function as transcription factors and their roles in development. Bioessays 22: 616-626.Google Scholar
  24. Khan J, Bittner M, Saal L, Teichmann U, Azorsa D, Gooden G, Pavan W, Trent J and Meltzer P (1999) cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. Proc Natl Acad Sci USA 96: 13,264-13,269.Google Scholar
  25. Kirby R, Hamilton G, Finnegan D, Johnson K and Jarman A (2001) Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required for muscle and gonad development. Curr Biol 11: 1044-1049.Google Scholar
  26. Klesert T, Cho D, Clark J, Maylie J, Adelman J, Snider L, Yuen E, Soriano P and Tapscott S (2000) Mice defficient in Six5 develop cataracts: implications for myotonic dystrophy. Nat Genet 25: 105-109.Google Scholar
  27. Klesert T, Otten A, Bird T and Tapscott S (1997) Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP. Nat Genet 16: 402-406.Google Scholar
  28. Kobayashi M, Nishikawa K, Suzuki T and Yamamoto M (2001) The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation. Dev Biol 232: 315-326Google Scholar
  29. Kumar J and Moses K (2001) EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification. Cell 104: 687-697.Google Scholar
  30. Lemyre E, Lemieux N, Decarie J and Lambert M (1998) Del(14) (q22.1q23.2) in a patient with anophthalmia and pituitary hypoplasia. Am J Med Genet 77: 162-165.Google Scholar
  31. Macfarlane W, McKinnon C, Felton-Edkins Z, Cragg H, James R and Docherty K (1999) Glucose stimulates translocation of the homeodomain transcription factor PDX1 from the cytoplasm to the nucleus in pancreatic β-cells. J Biol Chem 274: 1011-1016.Google Scholar
  32. O'Rahilly R and Muller F (1987) Developmental Stages in Human Embryos. University of California, Davis. Carnegi e Institution of Washington, publication 637.Google Scholar
  33. Ohto H, Kamada S, Tago K, Tominaga S, Ozaki H, Sato S and Kawakami K (1999) Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya. Mol Cell Biol 19: 6815-6824.Google Scholar
  34. Oliver G, Wehr R, Jenkins N, Copeland N, Cheyette B, Hartenstein V, Zipursky S and Gruss P (1995) Homeobox genes and connective tissue patterning. Development 121: 693-705.Google Scholar
  35. Ozaki H, Watanabe Y, Takahashi K, Kitamura K, Tanaka A, Urase K, Momoi T, Sudo K, Sakagami J, Asano M, Iwakura Y and Kawakami K (2001) Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development. Mol Cell Biol 21: 3343-3350.Google Scholar
  36. Ozaki H, Yamada K, Kobayashi M, Asakawa S, Minoshima S, Shimizu N, Kajitani M and Kawakami K (1999) Structure and chromosome mapping of the human SIX4 and murine Six4 genes. Cytogenet Cell Genet 87: 108-112.Google Scholar
  37. Pignoni F, Hu B, Zavitz K, Xiao J, Garrity P and Zipursky S (1997) The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell 91: 881-891.Google Scholar
  38. Rickard S, Parker M, van't Hoff W, Barnicoat A, Russell-Eggitt I, Winter R and Bitner-Glindzicz M (2001) Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM. Hum Genet 108: 398-403.Google Scholar
  39. Ridgeway A and Skerjanc I (2001) Pax3 is essential for skeletal myogenesis and the expression of six1 and eya2. J Biol Chem 276: 19,033-19,039.Google Scholar
  40. Sarkar P, Appukuttan B, Han J, Ito Y, Ai C, Tsai W, Chai Y, Stout J and Reddy S (2000) Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts. Nat Genet 25: 110-114.Google Scholar
  41. Sassoon D, Lyons G, Wright W, Lin V, Lassar A, Weintraub H and Buckingham M (1989) Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature 341: 303-307.Google Scholar
  42. Serikaku M and O'Tousa J (1994) sine oculis is a homeobox gene required for Drosophila visual system development. Genetics 138: 1137-1150.Google Scholar
  43. Spitz F, Demignon J, Porteu A, Kahn A, Concordet JP, Daegelen D and Maire P (1998) Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site. Proc Natl Acad Sci USA 95: 14,220-14,225.Google Scholar
  44. Spitz F, Salminen M, Demignon J, Kahn A, Daegelen D and Maire P (1997) A combination of MEF3 and NFI proteins activates transcription in a subset of fast-twitch muscles. Mol Cell Biol 17: 656-666.Google Scholar
  45. Tajbakhsh S and Buckingham M (1995) Lineage restriction of the myogenic conversion factor myf-5 in the brain. Development 121: 200-212.Google Scholar
  46. Tajbakhsh S and Buckingham M (2000) The birth of muscle progenitor cells in the mouse: spatiotemporal considerations. Curr Top Dev Biol 48: 225-268.Google Scholar
  47. Tassabehji M, Newton V, Leverton K, Turnbull K, Seemanova E, Kunze J, Sperling K, Strachan T and Read A (1994) PAX3 gene structure and mutations: close analogies between Waardenburg syndrome and the Splotch mouse. Hum Mol Genet 3: 26-30.Google Scholar
  48. Thornton C, Wymer J, Simmons Z, McClain C and Moxley RR (1997) Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene. Nat Genet 16: 407-409.Google Scholar
  49. Tiger CF, Fougerousse F, Grundstrom G, Velling T and Gullberg D (2001) α11β1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells. Dev Biol 237: 116-129.Google Scholar
  50. Winchester C, Ferrier R, Sermoni A, Clark B and Johnson K (1999) Characterization of the expression of DMPK and SIX5 in the human eye and implications for pathogenesis in myotonic dystrophy. Hum Mol Genet 8: 481-492.Google Scholar
  51. Xu PX, Adams J, Peters H, Brown M, Heaney S and Maas R (1999) Eya1-defficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet 23: 113-117.Google Scholar
  52. Xu PX, Woo I, Her H, Beier D and Maas R (1997a) Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode. Development 124: 219-231.Google Scholar
  53. Xu PX, Cheng J, Epstein JA and Maas RL (1997b) Mouse Eya genes are expressed during limb tendon development and encode a transcriptional activation function. Proc Natl Acad Sci USA 94: 11,974-11,979.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Françoise Fougerousse
    • 1
  • Muriel Durand
    • 1
  • Soledad Lopez
    • 2
  • Laurence Suel
    • 1
  • Josiane Demignon
    • 2
  • Charles Thornton
    • 3
  • Hidenori Ozaki
    • 4
  • Kyoshi Kawakami
    • 4
  • Patrick Barbet
    • 5
  • Jacques S. Beckmann
    • 6
  • Pascal Maire
    • 1
  1. 1.URA CNRS 1923, GénéthonEvryFrance
  2. 2.Département Génétique Développement et Pathologie Moleculaire, Institut Cochin, INSERM 567, CNRS 8104Université Paris VParisFrance
  3. 3.Department of Neurology, School of Medecine and DentistryUniversity of RochesterRochesterUSA
  4. 4.Department of BiologyJichi Medical schoolMinamikawachi, Kawachi, TochigiJapan
  5. 5.IFR CochinParisFrance
  6. 6.Weizmann Institute of ScienceRehovotIsrael

Personalised recommendations