Polycomb Limits the Neurogenic Competence of Neural Precursor Cells to Promote Astrogenic Fate Transition

Polycomb Limits the Neurogenic Competence of Neural Precursor Cells to Promote Astrogenic Fate Transition
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DOI:
10.1016/j.neuron.2009.08.021
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发表时间:
2009-09-10
期刊:
影响因子:
16.2
通讯作者:
Gotoh, Yukiko
Gotoh, Yukiko
中科院分区:
医学1区
文献类型:
--
作者:
Hirabayashi, Yusuke;Suzki, Nao;Gotoh, Yukiko

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在新皮层发育过程中,神经前体细胞(NPC或神经干细胞)首先产生神经元,然后产生星形胶质细胞。虽然从神经源性到星形的命运转换的时间对于确定神经元的数量至关重要,但其机制尚未完全了解。在这里,我们表明,polycomb组复合物(PcG)限制NPC的神经原性能力,并促进NPC的命运从神经源性向星形胶质细胞的转变。通过敲除Ring1B或Ezh2基因或Eed敲除使PcG失活,延长了NPC的神经发生期,并延迟了星形发育期的开始。此外,PcG被发现以发育阶段依赖的方式抑制原神经基因neurogenin1的启动子。这些结果证明了PcG的作用:NPC命运的时间调节。
During neocortical development, neural precursor cells (NPCs, or neural stem cells) produce neurons first and astrocytes later. Although the timing of the fate switch from neurogenic to astrogenic is critical for determining the number of neurons, the mechanisms are not fully understood. Here, we show that the polycomb group complex (PcG) restricts neurogenic competence of NPCs and promotes the transition of NPC fate from neurogenic to astrogenic. Inactivation of PcG by knockout of the Ring1B or Ezh2 gene or Eed knockdown prolonged the neurogenic phase of NPCs and delayed the onset of the astrogenic phase. Moreover, PcG was found to repress the promoter of the proneural gene neurogenin1 in a developmental-stage-dependent manner. These results demonstrate a role of PcG: the temporal regulation of NPC fate.