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Keywords:

  • atonal;
  • cortical plate;
  • helix-loop-helix factor;
  • neurogenesis;
  • proneural gene

Abstract

  1. Top of page
  2. Abstract
  3. References

In Drosophila, multiple helix-loop-helix (HLH) factors play an essential role in neural development. Mammalian homologues of such Drosophila HLH factors have been recently characterized and provide useful information for the analysis of the mechanisms of mammalian neurogenesis. We report here the molecular characterization of a novel mouse HLH factor, designated MATH-2, that has a structural homol-ogy to the product of Drosophila proneural gene atonal. MATH-2 consists of 337 amino acid residues and contains an atonal-related basic HLH domain. However, outside of this domain, there is no significant sequence similarity between MATH-2 and Atonal. MATH-2 expression occurs by embryonic day 11.5 (El 1.5), and is first detected in the wall of brain vesicles as well as in the spinal cord. It is expressed in the cortical plate and the mantle layer throughout the developing central nervous system but not in the ventricular zone. By E13.5, the expression becomes more prominent in the cortical plate of the cerebrum but decreases in the other regions. In the adult, the cerebrum produces a high level of MATH-2 RNA but other neural tissues produce only low levels. MATH-2 RNA is not detected in non-neural tissues, indicating that MATH-2 expression is specific to the nervous system. The gel mobility-shift analysis shows that MATH-2 can interact with several E-box sequences in collaboration with E47, a ubiquitously expressed HLH factor. These results raise the possibility that MATH-2 may be a Trans-acting factor involved in the development and maintenance of the mammalian nervous system.

Abbreviations
bHLH

basic helix-loop-helix

CNS

central nervous system

E

embryonic day

HLH

helix-looop-helix

P

postnatal day

References

  1. Top of page
  2. Abstract
  3. References
  • Akazawa, C., Sasai, Y., Nakanishi, S. & Kageyama, R. (1992) Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system, J. Biol. Chem. 267, 2187921885.
  • Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L. & Weintraub, H. (1990) The protein Id: A negative regulator of helix-loop-helix DNA binding proteins, Cell 61, 4959.
  • Braun, T., Rudnicki, M. A., Arnold, H.-H. & Jaenisch, R. (1992) Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death, Cell 71, 369382.
  • Campos-Ortega, J. A. & Jan, Y. N. (1991) Genetic and molecular bases of neurogenesis in Drosophila melanogaster, Annu. Rev. Neurosci. 14, 399420.
  • Christy, B. A., Sanders, L. K., Lau, L. F., Copeland, N. G., Jenkins, N. A. & Nathans, D. (1991) An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene, Proc. Natl Acad. Sci. USA 88, 18151819.
  • Davis, R. L., Weintraub, H. & Lassar, A. B. (1987) Expression of a single transfected cDNA converts fibroblasts to myoblasts, Cell 51, 9871000.
  • Duncan, M., DiCicco-Bloom, E. M., Xiang, X., Benezra, R. & Chada, K. (1992) The gene for the helix-loop-helix protein, Id, is specifically expressed in neural precursors, Dev. Biol. 154, 110.
  • Feder, J. N., Jan, L. Y. & Jan, Y. N. (1993) A rat gene with sequence homology to the Drosophila gene hairy is rapidly induced by growth factors known to influence neuronal differentiation, Mol. Cell. Biol. 13, 105113.
  • Guillemot, F., Lo, L.-C., Johnson, J. E., Auerbach, A., Anderson, D. J. & Joyner, A. L. (1993) Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons, Cell 75, 463476.
  • Guillemot, F. & Joyner, A. L. (1993) Dynamic expression of the murine achaete-scute homologue Mash-1 in the developing nervous system, Mech. Dev. 42, 171185.DOI: 10.1016/0925-4773(93)90006-J
  • Ishibashi, M., Sasai, Y., Nakanishi, S. & Kageyama, R. (1993) Molecular characterization of HES-2, a mammalian helix-loop-helix factor structurally related to Drosophila hairy and Enhancer of split, Eur. J. Biochem. 215, 645652.
  • Ishibashi, M., Moriyoshi, K., Sasai, Y., Shiota, K., Nakanishi, S. & Kageyama, R. (1994) Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system, EMBO J. 13, 17991805.
  • Jan, Y. N. & Jan, L. Y. (1993) HLH proteins, fly neurogenesis, and vertebrate myogenesis, Cell 75, 827830.
  • Jarman, A. P., Grau, Y., Jan, L. Y. & Jan, Y. N. (1993) atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system, Cell 73, 13071321.
  • Johnson, J. E., Birren, S. J. & Anderson, D. J. (1990) Two rat homologues of Drosophila achaete-scute specifically expressed in neuro-nal precursors, Nature 346, 858861.DOI: 10.1038/346858a0
  • Johnson, J. E., Birren, S. J., Saito, T. & Anderson, D. J. (1992) DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer, Proc. Natl Acad. Sci. USA 89, 35963600.
  • Kageyama, R., Sasai, Y. & Nakanishi, S. (1991) Molecular characterization of transcription factors that bind to the cAMP reponsive region of the substance P precursor gene: cDNA cloning of a novel C/EBP-related factor, J. Biol. Chem. 266, 1552515531.
  • Kohl, N. E., Legouy, E., DePinho, R. A., Nisen, P. D., Smith, R. K., Gee, C. E. & Alt, F. W. (1986) Human N-myc is closely related in organization and nucleotide sequence to c-myc, Nature 319, 7377.
  • Lee, C. C., Wu, X., Gibbs, R. A., Cook, R. G., Muzny, D. M. & Caskey, C. T. (1988) Generation of cDNA probes directed by amino acid sequence: Cloning of urate oxidase, Science 239, 12881291.
  • Lo, L.-C., Johnson, J. E., Wuenschell, C. W., Saito, T. & Anderson, D. J. (1991) Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells, Genes & Dev. 5, 15241537.
  • Neuman, T., Keen, A., Zuber, M. X., Kristjansson, G. I., Grass, P. & Nornes, H. O. (1993) Neuronal expression of regulatory helix-loop-helix factor Id2 gene in mouse, Dev. Biol. 160, 186195.DOI: 10.1006/dbio.1993.1297
  • Puelles, L. & Rubenstein, J. L. R. (1993) Expression patterns of homeo-box and other putative regulatory genes in the embryonic mouse forebrain suggest a neuromeric organization, Trends Neurosci. 16, 472479.DOI: 10.1016/0166-2236(93)90080-6
  • Rubenstein, J. L. R., Martinez, S., Shimamura, K. & Puelles, L. (1994) The embryonic vertebrate forebrain: the prosomeric model, Science 266, 578580.
  • Rudnicki, M. A., Braun, T., Hinuma, S. & Jaenisch, R. (1992) Inactiva-tion of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development, Cell 71, 383390.
  • Rudnicki, M. A., Schnegelsberg, P. N. J., Stead, R. H., Braun, T., Arnold, H.-H. & Jaenisch, R. (1993) MyoD or Myf-5 is required for the formation of skeletal muscle, Cell 75, 13511359.
  • Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B. & Erlich, H. A. (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase, Science 239, 487491.
  • Sakagami, T., Sakurada, K., Sakai, Y., Watanabe, T., Nakanishi, S. & Kageyama, R. (1994) Structure and chromosomal locus of the mouse gene encoding a cerebellar Purkinje cell-specific helix-loop-helix factor HES-3, Biochem. Biophys. Res. Commun. 203, 594601.DOI: 10.1006/bbrc.1994.2224
  • Sasai, Y., Kageyama, R., Tagawa, Y., Shigemoto, R. & Nakanishi, S. (1992) Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split, Genes & Dev. 6, 26202634.
  • Takebayashi, K., Sasai, Y., Sakai, Y., Watanabe, T., Nakanishi, S. & Kageyama, R. (1994) 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. 269, 51505156.
  • Takebayashi, K., Akazawa, C., Nakanishi, S. & Kageyama, R. (1995) Structure and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-5: Identification of the neural precursor cell-specific promoter element, J. Biol. Chem. 270, 13421349.DOI: 10.1074/jbc.270.3.1342
  • Wilkinson, D. G. (1993) in Essential developmental biology: a practical approach (Stern, C. D. & Holland, P. W. H., eds) pp. 257274, Oxford University Press, Oxford .
  • Zimmerman, K., Shih, J., Bars, J., Collazo, A. & Anderson, D. J. (1993) XASH-3, a novel Xenopus achaete-scute homolog, provides an early marker of planar neural induction and position along the mediolateral axis of the neural plate, Development 119, 221232.