Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology Zurich, 8093 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5807-12. doi: 10.1073/pnas.1013456108. Epub 2011 Mar 21.
Neural stem cells (NSCs) generate new granule cells throughout life in the mammalian hippocampus. Canonical Wnt signaling regulates the differentiation of NSCs towards the neuronal lineage. Here we identified the prospero-related homeodomain transcription factor Prox1 as a target of β-catenin-TCF/LEF signaling in vitro and in vivo. Prox1 overexpression enhanced neuronal differentiation whereas shRNA-mediated knockdown of Prox1 impaired the generation of neurons in vitro and within the hippocampal niche. In contrast, Prox1 was not required for survival of adult-generated granule cells after they had matured, suggesting a role for Prox1 in initial granule cell differentiation but not in the maintenance of mature granule cells. The data presented here characterize a molecular pathway from Wnt signaling to a transcriptional target leading to granule cell differentiation within the adult brain and identify a stage-specific function for Prox1 in the process of adult neurogenesis.
神经干细胞（NSCs）在哺乳动物海马体中终生产生新的颗粒细胞。经典 Wnt 信号通路调节 NSCs 向神经元谱系的分化。在这里，我们鉴定出富含 Pros 结构域的同源盒转录因子 Prox1 是β-catenin-TCF/LEF 信号通路在体外和体内的靶标。Prox1 的过表达增强了神经元的分化，而 shRNA 介导的 Prox1 敲低则损害了体外和海马龛内神经元的产生。相比之下，Prox1 并不需要成熟后成年生成的颗粒细胞的存活，这表明 Prox1 在初始颗粒细胞分化中起作用，但在成熟颗粒细胞的维持中不起作用。这里呈现的数据描绘了一条从 Wnt 信号到转录靶标导致成年大脑内颗粒细胞分化的分子途径，并确定了 Prox1 在成年神经发生过程中的特定阶段的功能。
