Epigenetic Regulation of Cortical Neuronal Lineage Progression

皮质放射状胶质细胞是一种神经干细胞，可以自我更新，并有序地产生各种类型的皮质神经元细胞 顺序的方式。在理解作为生物学基础的分子机制方面存在着根本性的差距。 神经元细胞类型的有序产生。我们的总体目标是了解内在的计时机制， 调节皮质神经发生过程中的细胞命运转变。我们已经确定了转录调节因子 Prdm 16（包含正调控域的16）作为精确调控 皮层神经发生过程中的定时细胞命运转换。我们对Prdm 16的研究可以作为一个切入点， 了解调节放射状神经胶质细胞分裂模式的相关遗传和表观遗传程序， 与神经元命运潜能的关系。在本提案中，我们计划利用MARIS（RNA分析方法 随后进行细胞内分选）以定义在细胞类型和阶段中由Prdm 16调节的分子程序 具体方式。我们还将确定PRDM 16结合的时间模式和顺式- 调节元件在皮层神经发生。我们的研究结果将直接影响 增加了我们对早期转录程序和染色质修饰的表达 会导致神经发育障碍

Cortical radial glia are neural stem cells that self renew and produce all cortical neuron cell types in an orderly sequential fashion. There is a fundamental gap in understanding the molecular mechanism that underlies the orderly production of neuronal cell types. Our overall goal is to understand the intrinsic timing mechanism that regulates cell fate transitions during cortical neurogenesis. We have identified the transcriptional regulator Prdm16 (Positive Regulatory Domain-containing 16) as being a critical component for regulating precisely timed cell fate transitions during cortical neurogenesis. Our studies of Prdm16 serve as an entry point to understanding the relevant genetic and epigenetic programs regulating the mode of radial glia cell division, and its relationship to neuronal fate potential. In this proposal we plan to utilize MARIS (Method for Analyzing RNA following Intracellular Sorting) to define the molecular programs regulated by Prdm16 in a cell type and stage specific manner. We will also determine the temporal pattern of PRDM16 binding and regulation of cis- regulatory elements during cortical neurogenesis. The finding from our studies will have a direct impact on increasing our understanding of how expression of early transcriptional programs and chromatin modifications can contribute to neurodevelopmental disorders.