Transcription factors governing the development of GHRH-neurons

项目摘要 Lee实验室的研究目标是破译指导胚胎发育的基因调控网络。 对小鼠下丘脑弓状核(ARC)中各种类型神经元的研究。ARC中的神经元 集中调节对生存和繁殖至关重要的各种动态平衡过程。尽管进行了广泛的研究 关于ARC神经元的生理作用，对其发育的基因调控程序很少 明白了。Lee实验室一直在通过成功地结合老鼠来开创这个具有挑战性的研究领域 遗传学和全基因组研究。特别是，Lee实验室完成了第一个用于染色质的芯片--Seq 免疫沉淀后测序)和scRNA-Seq(用于单细胞RNA-Seq)分析 发展中的ARC。有趣的是，许多ARC神经元有着共同的发育谱系。这很可能是 对于确保胚胎发育期间不同ARC神经元的平衡产生至关重要，使高度 在出生后的后期生活中对各种动态平衡过程的协调调节，如整合摄食， 繁衍和成长。通过对E15ARC进行scRNA-Seq，当ARC神经元活跃发育时，Le 实验室发现了极有可能在ARC神经元发育中发挥关键作用的转录因子。 其中包括信托基金Dlx1/2和Prox1，它们被认为在建立GHRH-- 神经元在其他相关ARC神经元谱系上的命运。通过使用一个集合验证这个假设 生化和细胞方法、小鼠遗传学和全基因组方法，Lee实验室希望推动 理解普通祖先如何被引导走上特定的谱系，而不是其他相关的ARC 神经元的命运，导致在胚胎发育过程中各种ARC神经元类型的平衡发展。

Project Summary The research goal of Lee lab is to decipher the gene regulatory network that directs the embryonic development of various types of neurons in the mouse arcuate nucleus of the hypothalamus (ARC). Neurons in the ARC centrally regulate various homeostatic processes critical for survival and reproduction. Despite extensive studies on the physiological roles of ARC neurons, the gene regulatory programs for their development are poorly understood. Lee lab has been pioneering this challenging area of studies by successfully combining mouse genetics and genome-wide studies. In particular, Lee lab accomplished the first ChIP-Seq (for chromatin immunoprecipitation followed by sequencing) and scRNA-Seq (for single cell RNA-Seq) analyses with developing ARC. Interestingly, many ARC neurons share common developmental lineages. This is likely to be critical to ensure the balanced production of different ARC neurons during embryogenesis, enabling a highly coordinated regulation of various homeostatic processes in later postnatal life, such as integration of feeding, reproduction, and growth. By performing scRNA-Seq with E15 ARC, when ARC neurons actively develop, Le lab identified transcription factors that are highly likely to play critical roles in the development of ARC neurons. These include the TFs Dlx1/2 and Prox1, which are hypothesized to play vital roles in establishing GHRH- neuronal fate over other related ARC neuronal lineages. By testing this hypothesis using an ensemble of biochemical and cellular methods, mouse genetics and genome-wide approaches, Lee lab wishes to advance the understanding of how common progenitors are guided to take a specific linage over other related ARC neuronal fates, resulting in the balanced development of various ARC neuronal types during embryogenesis.