The cell fate regulation mechanism during the development of neocortex controlled by the Hedgehog signaling.

新皮层由几种神经元亚型和神经胶质细胞组成。在皮质发生过程中，这些细胞的分化受到多种因素的调节。在本研究中，为了确认由形态因子Hedgehog （HH）信号控制的皮质发生机制，我们建立了条件敲除（cKO）小鼠，该小鼠在发育过程中在背端脑中抑制HH信号介质Smo的表达。HH信号通过调节细胞周期蛋白D2的表达来协调神经发生和细胞周期动力学。在Smo cKO小鼠中，第6b层表现出低可塑性，前额皮质多巴胺能神经元投射减少。这些结果表明，发育中的新皮层的组织学异常引起了神经网络的异常。

The neocortex comprises several neuronal subtypes and neural glial cells. Differentiation of these cells is regulated by various factors during corticogenesis. In this study, to confirm the mechanism of corticogenesis controlled by the morphogen Hedgehog (HH) signaling, we established conditional knockout (cKO) mice in which the expression of Smo, an HH-signaling mediator, was inhibited in the dorsal telencephalon during development. HH signaling coordinates neurogenesis and cell cycle kinetics via its regulation of cyclin D2 expression. In Smo cKO mice, layer 6b exhibited hypoplasticity with decreased dopaminergic neuronal projections in the prefrontal cortex. These findings suggest that the histologic anomalies in the developing neocortex induced neuronal network abnormalities.