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.

M Ishibashi , S Ang , K Shiota , S Nakanishi , R Kageyama , François Guillemot (1)

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

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.

Domaines: Biochimie, Biologie Moléculaire

M Ishibashi, S Ang, K Shiota, S Nakanishi, R Kageyama, et al.. 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.. Genes and Development, 1995, 9 (24), pp.3136-3148. ⟨10.1101/gad.9.24.3136⟩. ⟨hal-03951399⟩