FoxP2 透過PDGF 訊息傳導路徑調控PI9 細胞的神經元分化

Abstract

FoxP2 是第一個被發現與人類語言能力有關的基因，此基因在脊椎動物中有高度保守性。在成年鳴禽中，前腦的側腦室區新生成的神經前驅細胞會移動到與學習唱歌有關的區域Area X ，並在這區成分化成神經元。側腦室區的神經前驅細胞及AreaX 的新生神經元都有FoxP2 的表現，這晴示著FoxP2 可能會調控神經元新生，但其機制仍未明暸。前人研究發現Platelet-derived growth factorreceptorα(PDGFRα) 可能是FoxP2 的下游基因。PDGF 會促進小鼠側腦室下區的神經幹細胞增生，並產生新的寡樹突細胞。因此我們假設FoxP2 可能是透過PDGFRα 來調控神經元新生。我們的實驗結果顯示FoxP2 會抑制P19 細胞的神經元分化，且比現象可被PDGFRα 抑制劑所反轉。此結果顯示FoxP2 會透過PDGFRα 來調控神經元分化。

FoxP2 is a transcription factor involved in vocal behaviors. During adult neurogenesis in songbirds, FoxP2 is expressed by neural progenitor cells and newly generated neurons in Area X, an area for song learning. However, whether FoxP2 regulates neurogenesis and the mechanism remain unclear. We tested this hypothesis by overexpressing FoxP2 in a mouse embryonic carcinoma cell line P19 to examine whether it regulates neurogenesis. We found that FoxP2 did not promote neuronal differentiation. We also identified that Platelet-derived growth factor (PDGF) pathway could be one of the downstream effector ofFoxP2 during neuronal differentiation. Taken together, FoxP2 may play important roles during neural development. A better understanding of neurogenesis in the mammalian brain should provide insight into regulatory mechanisms and lead to strategies for brain repair.