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Notch1 and Notch2 collaboratively maintain radial glial cells in mouse neurogenesis
Neuroscience Research ( IF 2.9 ) Pub Date : 2020-12-11 , DOI: 10.1016/j.neures.2020.11.007
Shun Mase 1 , Atsunori Shitamukai 2 , Quan Wu 2 , Mitsuru Morimoto 3 , Thomas Gridley 4 , Fumio Matsuzaki 1
Affiliation  

During mammalian corticogenesis, Notch signaling is essential to maintain neural stem cells called radial glial cells (RGCs) and the cortical architecture. Because the conventional knockout of either Notch1 or Notch2 causes a neuroepithelial loss prior to neurogenesis, their functional relationship in RGCs remain elusive. Here, we investigated the impacts of single knockout of Notch1 and Notch2 genes, and their conditional double knockout (DKO) on mouse corticogenesis. We demonstrated that Notch1 single knockout affected RGC maintenance in early to mid-neurogenesis whereas Notch2 knockout caused no apparent defect. In contrast, Notch2 plays a role in the RGC maintenance as Notch1 does at the late stage. Notch1 and Notch2 DKO resulted in the complete loss of RGCs, suggesting their cooperative function. We found that Notch activity in RGCs depends on the Notch gene dosage irrespective of Notch1 or Notch2 at late neurogenic stage, and that Notch1 and Notch2 have a similar activity, most likely due to a drastic increase in Notch2 transcription. Our results revealed that Notch1 has an essential role in establishing the RGC pool during the early stage, whereas Notch1 and Notch2 subsequently exhibit a comparable function for RGC maintenance and neurogenesis in the late neurogenic period in the mouse telencephalon.



中文翻译:

Notch1 和 Notch2 在小鼠神经发生中协同维持径向神经胶质细胞

在哺乳动物皮质发生过程中,Notch 信号传导对于维持称为径向神经胶质细胞 (RGC) 的神经干细胞和皮质结构至关重要。由于Notch1Notch2的常规敲除在神经发生之前导致神经上皮损失,因此它们在 RGC 中的功能关系仍然难以捉摸。在这里,我们研究了Notch1Notch2基因的单敲除及其条件性双敲除 (DKO) 对小鼠皮质发生的影响。我们证明了Notch1单敲除影响神经发生早期到中期的 RGC 维持,而Notch2敲除没有引起明显缺陷。相比之下,Notch2Notch1在后期一样在RGC维护中发挥作用。Notch1Notch2 DKO 导致 RGC 完全丧失,表明它们的合作功能。我们发现 RGC 中的 Notch 活性取决于Notch基因剂量,而与神经发生晚期的Notch1Notch2 无关,并且Notch1Notch2具有相似的活性,很可能是由于Notch 2 转录的急剧增加。我们的结果表明,Notch1在早期阶段在建立 RGC 池中起着至关重要的作用,而Notch1Notch2 随后在小鼠端脑的神经发生晚期表现出类似的 RGC 维持和神经发生功能。

更新日期:2020-12-11
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