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研究揭示皮层中间神经元发育的遗传和表观遗传协调
作者:小柯机器人 发布时间:2021/9/24 14:27:36

美国哈佛医学院Gord Fishell、纽约大学Richard Bonneau等研究人员合作揭示皮层中间神经元发育的遗传和表观遗传协调。2021年9月22日,国际知名学术期刊《自然》在线发表了这一成果。

据研究人员介绍,大脑皮层的特点之一是中间神经元的极端多样性。皮层中间神经元的两个最大亚型,即小清蛋白和生长抑素阳性的细胞,在成年后在形态和功能上是不同的,但在内侧神经节突起中产生于共同的谱系。这使得它们成为研究细胞多样性产生的一个有力模型。

研究人员揭示了转录和染色质结构的发育变化如何使这些细胞在小鼠皮层中获得不同的身份。通用的神经元特征在细胞周期退出时通过远端元件的染色质开放而被首次检测到。通过构建细胞类型的基因调控网络,研究人员观察到小清蛋白和生长抑素阳性细胞在皮层内定居时启动了不同的程序。研究人员用这些网络来模拟了一个共同调节因子Mef2c的不同转录要求,并通过实验性功能缺失实验证实了预测的准确性。因此,研究人员揭示了一个共同的分子程序是如何分化的,进而使得这些神经元亚型在成年后获得高度分化的特性。

这个方法提供了一个框架来研究细胞多样性的出现,以及量化和预测候选基因对细胞类型特定发育的影响。

附:英文原文

Title: Genetic and epigenetic coordination of cortical interneuron development

Author: Allaway, Kathryn C., Gabitto, Mariano I., Wapinski, Orly, Saldi, Giuseppe, Wang, Chen-Yu, Bandler, Rachel C., Wu, Sherry Jingjing, Bonneau, Richard, Fishell, Gord

Issue&Volume: 2021-09-22

Abstract: One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons1,2,3. The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence4,5,6,7,8,9,10,11. This makes them an attractive model for studying the generation of cell diversity. Here we examine how developmental changes in transcription and chromatin structure enable these cells to acquire distinct identities in the mouse cortex. Generic interneuron features are first detected upon cell cycle exit through the opening of chromatin at distal elements. By constructing cell-type-specific gene regulatory networks, we observed that parvalbumin- and somatostatin-positive cells initiate distinct programs upon settling within the cortex. We used these networks to model the differential transcriptional requirement of a shared regulator, Mef2c, and confirmed the accuracy of our predictions through experimental loss-of-function experiments. We therefore reveal how a common molecular program diverges to enable these neuronal subtypes to acquire highly specialized properties by adulthood. Our methods provide a framework for examining the emergence of cellular diversity, as well as for quantifying and predicting the effect of candidate genes on cell-type-specific development.

DOI: 10.1038/s41586-021-03933-1

Source: https://www.nature.com/articles/s41586-021-03933-1

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html