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
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
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DOI：
10.1101/gad.9.24.3136
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发表时间：
1995-12-15
影响因子：
10.5
通讯作者：
Guillemot, F
中科院分区：
文献类型：
--
作者：
Ishibashi, M;Ang, SL;Guillemot, F
哺乳动物HES-1基因编码一种螺旋-环-螺旋(HLH)因子，被认为是神经发生的负调控因子。为了直接研究HES-1在哺乳动物胚胎发育中的功能，我们对HES-1基因进行了定向干扰。突变纯合子的小鼠表现出严重的神经发育缺陷，并在怀孕期间或出生后死亡。在HES-1缺失型胚胎的发育脑中，神经分化因子Mash-1和其他神经HLH因子的表达上调，并过早出现有丝分裂后神经元。这些结果表明，HES-I正常控制神经发生的适当时机，并调节神经管的形态发生。
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-I normally controls the proper timing of neurogenesis and regulates neural tube morphogenesis.