Transcriptional profiling of sequentially generated septal neuron fates.
Transcriptional profiling of sequentially generated septal neuron fates.
复制标题
顺序生成的间隔神经元命运的转录谱。
DOI：
10.7554/elife.71545
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发表时间：
2021-12-01
期刊：
影响因子：
7.7
通讯作者：
Harwell CC
中科院分区：
文献类型：
--
作者：
Turrero García M;Stegmann SK;Lacey TE;Reid CM;Hrvatin S;Weinreb C;Adam MA;Nagy MA;Harwell CC
隔膜是腹侧前脑结构，已知调节先天行为。在胚胎发育过程中，隔神经元在多个增殖区域中从神经祖细胞产生，这些神经祖细胞遵循仍然在很大程度上未知的转录程序。在这里，我们使用单细胞RNA测序，组织学和遗传模型的组合，以解决如何间隔神经元的多样性是建立在神经发生。我们发现隔祖细胞的转录谱随着神经发生的沿着变化，与不同神经元类型的产生相一致。我们的特点隔隆起，解剖学上不同的和短暂的增殖区组成的祖细胞具有独特的分子概况，增殖能力和命运的潜力相比，喙隔祖细胞区。我们发现，Nkx2.1表达隔隆起祖细胞产生的神经元属于至少三个形态类，出生在时间队列分布在不同的隔核中的顺序喷泉样模式。我们的研究提供了对控制隔膜中不同神经元类型顺序产生的分子程序的深入了解，隔膜是一种在调节情绪和动机方面具有重要作用的结构。
The septum is a ventral forebrain structure known to regulate innate behaviors. During embryonic development, septal neurons are produced in multiple proliferative areas from neural progenitors following transcriptional programs that are still largely unknown. Here, we use a combination of single-cell RNA sequencing, histology, and genetic models to address how septal neuron diversity is established during neurogenesis. We find that the transcriptional profiles of septal progenitors change along neurogenesis, coinciding with the generation of distinct neuron types. We characterize the septal eminence, an anatomically distinct and transient proliferative zone composed of progenitors with distinctive molecular profiles, proliferative capacity, and fate potential compared to the rostral septal progenitor zone. We show that Nkx2.1-expressing septal eminence progenitors give rise to neurons belonging to at least three morphological classes, born in temporal cohorts that are distributed across different septal nuclei in a sequential fountain-like pattern. Our study provides insight into the molecular programs that control the sequential production of different neuronal types in the septum, a structure with important roles in regulating mood and motivation.