Generation of neurons in the embryonic neocortex is a balanced process of proliferation and differentiation of neuronal progenitor cells. Canonical Wnt signalling is crucial for expansion of radial glial cells in the ventricular zone and for differentiation of intermediate progenitors in the subventricular zone. We detected abundant expression of two transcrtiption factors mediating canonical Wnt signalling, Tcf7L1 and Tcf7L2, in the ventricular zone of the embryonic neocortex. Conditional knock-out analysis showed that Tcf7L2, but not Tcf7L1, is the principal Wnt mediator important for maintenance of progenitor cell identity in the ventricular zone. In the absence of Tcf7L2, the Wnt activity is reduced, ventricular zone markers Pax6 and Sox2 are downregulated and the neuroepithelial structure is severed due to the loss of apical adherens junctions. This results in decreased proliferation of radial glial cells, the reduced number of intermediate progenitors in the subventricular zone and hypoplastic forebrain. Our data show that canonical Wnt signalling, which is essential for determining the neuroepithelial character of the neocortical ventricular zone, is mediated by Tcf7L2.

中文翻译：

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Tcf7L2对于正在发育的小鼠新皮层中的神经发生至关重要。

胚胎新皮层中神经元的产生是神经元祖细胞增殖和分化的平衡过程。规范的Wnt信号对于心室区放射状神经胶质细胞的扩张以及心室下区中间祖细胞的分化至关重要。我们在胚胎新皮层的心室区中检测到两种介导经典Wnt信号传递的转录因子Tcf7L1和Tcf7L2的大量表达。条件性基因敲除分析表明，Tcf7L2（而非Tcf7L1）是主要的Wnt介体，对维持心室区祖细胞的身份很重要。在没有Tcf7L2的情况下，Wnt活性会降低，心室区标志Pax6和Sox2被下调，并且神经上皮结构由于根尖黏附连接的丧失而被切断。这导致放射状神经胶质细胞的增殖减少，脑室下区域的中间祖细胞数量减少和前体发育不良。我们的数据表明，典型的Wnt信号传导是Tcf7L2介导的，这对于确定新皮层心室区的神经上皮特征至关重要。