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Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects.

Mammalian hairy and Enhancer of split homolog-1 (HES-1) encodes a helix-loop-helix (HLH) factor that is thought to act as a negative regulator of neurogenesis. To directly investigate the functions of HES-1 in mammalian embryogenesis, we performed a targeted disruption of the HES-1 locus. Mice homozygous for the mutation exhibited severe neurulation defects and died during gestation or just after birth. In the developing brain of HES-1-null embryos, expression of the neural differentiation factor Mash-1 and other neural HLH factors was up-regulated and postmitotic neurons appeared prematurely. These results suggest that HES-1 normally controls the proper timing of neurogenesis and regulates neural tube morphogenesis.

Pubmed ID: 8543157


  • Ishibashi M
  • Ang SL
  • Shiota K
  • Nakanishi S
  • Kageyama R
  • Guillemot F


Genes & development

Publication Data

December 15, 1995

Associated Grants


Mesh Terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA Primers
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Embryonic and Fetal Development
  • Helix-Loop-Helix Motifs
  • Insect Hormones
  • Insect Proteins
  • Mice
  • Molecular Sequence Data
  • Nervous System
  • Neural Tube Defects
  • Repressor Proteins
  • Transcription Factors
  • Up-Regulation