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Wnt signalling regulates adult hippocampal neurogenesis

机译：Wnt信号调节成年海马神经发生

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The generation of new neurons from neural stem cells is restricted to two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyrus. In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population. The identity of these signals is largely unknown. Here we show that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development. We also show that the Wnt/β-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche. Overexpression of Wnt3 is sufficient to increase neurogenesis from AHPs in vitro and in vivo. By contrast, blockade of Wnt signalling reduces neurogenesis from AHPs in vitro and abolishes neurogenesis almost completely in vivo. Our data show that Wnt signalling is a principal regulator of adult hippocampal neurogenesis and provide evidence that Wnt proteins have a role in adult hippocampal function.
机译：由神经干细胞产生的新神经元仅限于成年哺乳动物中枢神经系统的两个区域：侧脑室的脑室下区和海马齿状回的颗粒下区。在这两个区域，微环境提供的信号调节了局部干细胞群体的维持，增殖和神经元命运。这些信号的身份在很大程度上是未知的。在这里，我们显示成年海马干/祖细胞（AHP）表达Wnt蛋白的受体和信号成分，Wnt蛋白是胚胎发育中神经干细胞行为的关键调节剂。我们还表明，Wnt /β-catenin途径是活跃的，Wnt3在海马神经源性利基表达。 Wnt3的过表达足以增加体外和体内AHP的神经发生。相比之下，Wnt信号传导的阻断在体外减少了AHP的神经发生，并在体内几乎完全消除了神经发生。我们的数据表明Wnt信号是成人海马神经发生的主要调节器，并提供Wnt蛋白在成人海马功能中起作用的证据。

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