View the Current Issue

Article

  • The EMBO Journal (1999) 18, 2196 - 2207
  • doi:10.1093/emboj/18.8.2196

Hes1 and Hes5 as Notch effectors in mammalian neuronal differentiation

Toshiyuki Ohtsuka1,2,7, Makoto Ishibashi2,3,4,5,7, Gérald Gradwohl6,7, Shigetada Nakanishi2, François Guillemot6 and Ryoichiro Kageyama1,2

  1. Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan
  2. Department of Biological Sciences, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8501, Japan
  3. Department of Anatomy, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8501, Japan
  4. Inheritance and Variation, PRESTO, Japan Science and Technology Corporation, Kyoto 606-8501, Japan
  5. Present address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
  6. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur/Collège de France, Illkirch, CU de Strasbourg, France
  7. T.Ohtsuka, M.Ishibashi and G.Gradwohl contributed equally to this work

Correspondence to:

François GuillemotRyoichiro Kageyama, E-mail: rkageyam@virus.kyoto-u.ac.jp

Received 10 December 1998; Accepted 25 February 1999; Revised 25 February 1999

While the transmembrane protein Notch plays an important role in various aspects of development, and diseases including tumors and neurological disorders, the intracellular pathway of mammalian Notch remains very elusive. To understand the intracellular pathway of mammalian Notch, the role of the bHLH genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologues) was examined by retrovirally misexpressing the constitutively active form of Notch (caNotch) in neural precursor cells prepared from wild-type, Hes1-null, Hes5-null and Hes1-Hes5 double-null mouse embryos. We found that caNotch, which induced the endogenous Hes1 and Hes5 expression, inhibited neuronal differentiation in the wild-type, Hes1-null and Hes5-null background, but not in the Hes1-Hes5 double-null background. These results demonstrate that Hes1 and Hes5 are essential Notch effectors in regulation of mammalian neuronal differentiation.

  • Keywords:

    • bHLH,
    • Hes1,
    • Hes5,
    • neuronal differentiation,
    • Notch