Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium
Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium
复制标题
DOI：
10.1242/dev.095018
复制
发表时间：
2013-08-15
期刊：
影响因子：
4.6
通讯作者：
Bally-Cuif, Laure
中科院分区：
文献类型：
--
作者：
Alunni, Alessandro;Krecsmarik, Monika;Bally-Cuif, Laure
维持成体器官生发区的内稳态是一个基本的，但在机制上却知之甚少的过程。特别是，控制干细胞激活的因素仍不清楚。我们之前已经证明Notch信号限制了成年斑马鱼苍白膜中的神经干细胞（NSC）增殖。结合药理学和遗传学操作，我们在这里证明了长期Notch失效主要通过从静止激活和增加对称分裂的发生来诱导NSC扩增。表达分析、morpholino介导的失效和Notch3 -null突变体的产生直接表明Notch3参与了这些作用。相反，notch1b功能的缺失导致神经元的生成，而激活的NSC状态则被破坏。总之，我们的结果支持Notch受体在NSC招募的连续步骤中的不同参与。他们认为Notch3位于这一层次结构的顶端，控制着NSC的激活和扩增，在生理条件下保护成年NSC储存库的稳态。
Maintaining the homeostasis of germinal zones in adult organs is a fundamental but mechanistically poorly understood process. In particular, what controls stem cell activation remains unclear. We have previously shown that Notch signaling limits neural stem cell (NSC) proliferation in the adult zebrafish pallium. Combining pharmacological and genetic manipulations, we demonstrate here that long-term Notch invalidation primarily induces NSC amplification through their activation from quiescence and increased occurrence of symmetric divisions. Expression analyses, morpholino-mediated invalidation and the generation of a notch3-null mutant directly implicate Notch3 in these effects. By contrast, abrogation of notch1b function results in the generation of neurons at the expense of the activated NSC state. Together, our results support a differential involvement of Notch receptors along the successive steps of NSC recruitment. They implicate Notch3 at the top of this hierarchy to gate NSC activation and amplification, protecting the homeostasis of adult NSC reservoirs under physiological conditions.