Foxg1调节皮层中间神经元的发育

发布时间：2018-03-28 10:57

本文选题：Dlx1/2　切入点：Foxg1　出处：《东南大学》2016年博士论文

【摘要】：尽管中间神经元在调节皮层功能中起着关键性的作用,但对于皮层中间神经元的发育调控机制目前还知之甚少。本课题探讨转录因子Foxg1在中间神经元发育过程中的作用。通过将Foxg1fl/fl和Dlx5/6-Cre小鼠进行交配从而在腹侧端脑条件性敲除Foxg1基因,结果导致中间神经元发育的异常。在发育中的中间神经元中敲除了 Foxg1后,多种迁移相关受体分子,包括:roundabout-1,Eph receptor A4和C-X-C motif receptor 4/7的表达水平均出现下降,而这可能是导致这些中间神经元出现迁移障碍的原因。除此之外,前人报道过的参与中间神经元发育的转录因子Dlx1/2和Mash1的mRNA表达水平也显著上调。而与野生型相比这些敲除了Foxg1的中间神经元发育出的神经突起更短,分支变少,且其体外的迁移能力也受到了严重的影响。另一个有趣的发现是,通常被认为是发育中兴奋性神经元的重要调节分子的转录因子Prox1在mRNA和蛋白水平上都出现了明显的上调,这提示了 Prox1可能在中间神经元发育过程中也起到关键性的作用。综上所述,我们的实验结果表明Foxg1作为Dlx1/2,Mash1和Prox1的上游调节分子,在控制中间神经元发育中可能起着重要的作用。以上这些发现有利于我们进一步了解中间神经元发育的分子机制。
[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.
【学位授予单位】：东南大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R338

【相似文献】