Department of Life Science, National Taiwan Normal University, Taipei, 116, Taiwan.
Dev Neurobiol. 2014 Jul;74(7):723-38. doi: 10.1002/dneu.22166. Epub 2014 Feb 18.
Mutations of the transcription factor FOXP2 in humans cause a severe speech and language disorder. Disruption of Foxp2 in songbirds or mice also leads to deficits in song learning or ultrasonic vocalization, respectively. These data suggest that Foxp2 plays important roles in the developing nervous system. However, the mechanism of Foxp2 in regulating neural development remains elusive. In the current study, we found that Foxp2 increased neuronal differentiation without affecting cell proliferation and cell survival in primary neural progenitors from embryonic forebrains. Foxp2 induced the expression of platelet-derived growth factor receptor α, which mediated the neurognic effect of Foxp2. In addition, Foxp2 positively regulated the differentiation of medium spiny neurons derived from the lateral ganglionic eminence and negatively regulated the formation of interneurons derived from dorsal medial ganglionic eminence by interacting with the Sonic hedgehog pathway. Taken together, our results suggest that Foxp2 regulates multiple aspects of neuronal development in the embryonic forebrain.
人类转录因子 FOXP2 的突变会导致严重的言语和语言障碍。在鸣禽或小鼠中破坏 Foxp2 也分别导致歌唱学习或超声发声的缺陷。这些数据表明 Foxp2 在发育中的神经系统中发挥着重要作用。然而，Foxp2 调节神经发育的机制仍不清楚。在本研究中，我们发现 Foxp2 增加了神经元分化，而不影响胚胎前脑原代神经祖细胞的细胞增殖和细胞存活。Foxp2 诱导血小板衍生生长因子受体 α 的表达，该受体介导了 Foxp2 的神经发生作用。此外，Foxp2 通过与 Sonic hedgehog 通路相互作用，正向调节来自外侧神经节隆起的中型多棘神经元的分化，并负向调节来自背内侧神经节隆起的中间神经元的形成。总之，我们的结果表明 Foxp2 调节胚胎前脑的多个神经元发育方面。
