在中枢神经系统的发育过程中，室区的神经干细胞先生成不同种类的神经元，再生成星形胶质细胞和少突胶质细胞。发育神经生物学的一个基本问题是：究竟有什么信号或因子控制着神经干细胞的神经元生成向胶质细胞生成的转变。我们已发表的研究表明WNT信号通路被激活后，少突胶质细胞的生成被抑制，而星形胶质细胞的生成也可能减少。我们因此推测WNT可能是重要的胶质细胞生成抑制信号。由此开展的前期试验表明WNT信号通路可能通过促进Ngn2的表达抑制胶质细胞生成。我们拟先通过体内基因突变小鼠分析WNT信号通路在胶质细胞生成中的功能，并追踪神经干细胞的命运。接着筛选WNT信号通路的靶基因，并通过鸡胚电转实验验证靶基因在胶质细胞生成的功能。本项目的完成，能够使我们深入了解神经元生成向胶质细胞生成的转变机制，为神经元的再生研究提供一定的基础。

During the development of central nervous system (CNS), neural stem cells in the ventricular zone firstly give rise to various types of neurons, followed by astrocytes and oligodendrocytes. What signals or factors control the developmental switch from neurogenesis to gliogenesis remains one of the fundamental questions in developmental neurobiology. Our recent study showed that activation of WNT signaling inhibits the generation of oligodendrocyte progenitor cells, and astrocyte precursors as well. We thus hypothesize that WNT signaling may play important roles in the inhibition of gliogenesis. Consistent with this hypothesis, our preliminary experiments showed that the inhibition of gliogenesis by WNT signaling is probably mediated by the up-regulation of Ngn2. In this proposal, we will use various mutant mice to study the functions of WNT signaling during the neuron-to-glia switch, and trace the fate of neural stem cells after modifying the WNT signaling. We will also screen the target genes of WNT signaling, and examine their functions in gliogenesis using in ovo electroporation assays. This study will provide important insights into the molecular mechanisms underlying the switch from neurogenesis to gliogenesis, and facilitate the design of molecular strategies to promote neural regeneration in injured or diseased neural tissues.