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.
Institute for Immunology, Kyoto University Faculty of Medicine, Japan.
M
M
Ishibashi
S L
SL
Ang
K
K
Shiota
S
S
Nakanishi
R
R
Kageyama
F
F
Guillemot
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs; D007301:Insect Hormones / Q000235:genetics*; D019476:Insect Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009420:Nervous System / Q000166:cytology / Q000196:embryology*; D009436:Neural Tube Defects / Q000235:genetics*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; D019476:Insect Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C084530:E(spl)mdelta-HLH protein, Drosophila; C061841:hairy protein, insect