本文選題：Dlx1/2　切入點：Foxg1　出處：《東南大學》2016年博士論文

【摘要】：盡管中間神經(jīng)元在調節(jié)皮層功能中起著關鍵性的作用,但對于皮層中間神經(jīng)元的發(fā)育調控機制目前還知之甚少。本課題探討轉錄因子Foxg1在中間神經(jīng)元發(fā)育過程中的作用。通過將Foxg1fl/fl和Dlx5/6-Cre小鼠進行交配從而在腹側端腦條件性敲除Foxg1基因,結果導致中間神經(jīng)元發(fā)育的異常。在發(fā)育中的中間神經(jīng)元中敲除了 Foxg1后,多種遷移相關受體分子,包括:roundabout-1,Eph receptor A4和C-X-C motif receptor 4/7的表達水平均出現(xiàn)下降,而這可能是導致這些中間神經(jīng)元出現(xiàn)遷移障礙的原因。除此之外,前人報道過的參與中間神經(jīng)元發(fā)育的轉錄因子Dlx1/2和Mash1的mRNA表達水平也顯著上調。而與野生型相比這些敲除了Foxg1的中間神經(jīng)元發(fā)育出的神經(jīng)突起更短,分支變少,且其體外的遷移能力也受到了嚴重的影響。另一個有趣的發(fā)現(xiàn)是,通常被認為是發(fā)育中興奮性神經(jīng)元的重要調節(jié)分子的轉錄因子Prox1在mRNA和蛋白水平上都出現(xiàn)了明顯的上調,這提示了 Prox1可能在中間神經(jīng)元發(fā)育過程中也起到關鍵性的作用。綜上所述,我們的實驗結果表明Foxg1作為Dlx1/2,Mash1和Prox1的上游調節(jié)分子,在控制中間神經(jīng)元發(fā)育中可能起著重要的作用。以上這些發(fā)現(xiàn)有利于我們進一步了解中間神經(jīng)元發(fā)育的分子機制。
[Abstract]:Although intermediate neurons play a key role in regulating cortical function, However, little is known about the developmental regulation mechanism of cortical interneuron. In this study, we explored the role of transcription factor Foxg1 in the development of interneuron. By mating Foxg1fl/fl and Dlx5/6-Cre mice, we found the ventral end of the brain. Piecemeal knockout of the Foxg1 gene, The results showed that after knockout of Foxg1 in the developing interneuron, the expression levels of various transportation-related receptor molecules, including the expression of C-X-C round-about-1Eph receptor A4 and C-X-C motif receptor 4 / 7, decreased after knockout in the developing interneuron. And this may be the reason why these intermediate neurons have a migration problem. In addition, The mRNA expression of transcription factors Dlx1/2 and Mash1 involved in the development of intermediate neurons was also significantly up-regulated by previous reports. Compared with the wild type, the neurons with Foxg1 knockout produced shorter neurites and fewer branches. Another interesting finding is that the transcription factor Prox1, which is generally considered to be an important regulatory molecule of developmental excitatory neurons, is significantly up-regulated at the mRNA and protein levels. This suggests that Prox1 may also play a key role in the development of intermediate neurons. In conclusion, our results suggest that Foxg1 acts as the upstream regulator of Dlx1 / 2 Mash1 and Prox1. These findings may play an important role in controlling the development of intermediate neurons, and these findings are helpful for us to further understand the molecular mechanism of the development of intermediate neurons.
【學位授予單位】：東南大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R338

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