Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, 23 Matsuokashimoaizuki, Eiheiji, Fukui 910-1193, Japan.
Neurosci Lett. 2013 Jun 28;547:87-91. doi: 10.1016/j.neulet.2013.05.006. Epub 2013 May 13.
Translocation of the Smoothened to the cell membrane is critical for sonic hedgehog activity. However, the biological importance of Smoothened itself has not been fully studied. To address this issue, we disabled Smoothened specifically in the dorsal telencephalon. Birth-date analysis and layer marker expression patterns revealed the slightly impaired development of the superficial layer neurons in the embryos of Emx1-Cre; Smoothened(fl/-) conditional knockout mice. Further analysis of the mutant embryos revealed a decrease in the number of intermediate progenitor cells. In the knockout mice, the expression of cyclin D2, but not cyclin D1 or cyclin E, was reduced in the dorsal telencephalon. In addition, the projections of dopaminergic neurons were affected during development, and the number of activated astrocytes was increased in the neocortex of the mutant mice. Our data suggest that Smoothened signaling, acting through cyclin D2, is critical for the proper development and maturation of the neocortex.
Smoothened 向细胞膜的易位对于 sonic hedgehog 活性至关重要。然而，Smoothened 本身的生物学重要性尚未得到充分研究。为了解决这个问题，我们在背侧端脑特异性地使 Smoothened 失活。出生时间分析和层标记表达模式揭示了 Emx1-Cre；Smoothened(fl/-)条件性敲除小鼠胚胎中浅层神经元的发育略有受损。对突变体胚胎的进一步分析显示中间祖细胞数量减少。在敲除小鼠中，cyclin D2 的表达，而不是 cyclin D1 或 cyclin E，在背侧端脑中减少。此外，多巴胺能神经元的投射在发育过程中受到影响，并且突变小鼠新皮层中的活化星形胶质细胞数量增加。我们的数据表明，Smoothened 信号通过 cyclin D2 发挥作用，对于新皮层的正常发育和成熟至关重要。
