具有发散投影模式的神经元的多组学分析确定了轴突寻路的新调节器,Advanced Science

当前位置： X-MOL 学术 › Adv. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

具有发散投影模式的神经元的多组学分析确定了轴突寻路的新调节器
Advanced Science ( IF 14.3 ) Pub Date : 2022-08-21 , DOI: 10.1002/advs.202200615
Marta Fernández-Nogales ₁ , Maria Teresa López-Cascales ₁ , Verónica Murcia-Belmonte ₁ , Augusto Escalante ₁ , Jordi Fernández-Albert ₁ , Rafael Muñoz-Viana ₁ , Angel Barco ₁ , Eloísa Herrera ₁

Affiliation

轴突寻路是神经回路形成的关键步骤。然而，调节其进展的转录机制仍然知之甚少。一些神经元轴突在发育过程中穿过或避开中线的二元决定代表了一个强大的模型，用于研究控制轴突轨迹选择的机制。在这里，为了确定轴突引导的新调节因子，这项工作比较了两个神经元亚群的转录组和染色质占据谱，同侧 (iRGC) 和对侧视网膜神经节细胞 (cRGC)，具有相似的功能但不同的轴突轨迹。这些分析检索了许多编码先前未涉及轴突寻路的蛋白质的基因。体内功能实验证实了其中一些候选物在轴突导航中的意义。γ-突触核蛋白被确定为诱导中线交叉所必需的。足迹和荧光素酶测定表明，这种小型蛋白质受 cRGC 中的转录因子 (TF) Pou4f1 调节。还表明 Lhx2/9 在 iRGC 中特异性表达，并控制与 Zic2 调节的程序部分重叠的程序，先前描述为 iRGC 规范的必要条件。总体而言，这些分析确定了数十种可能参与轴突导向的新分子，并揭示了选择轴突轨迹背后的调控逻辑。

"点击查看英文标题和摘要"

Multiomic Analysis of Neurons with Divergent Projection Patterns Identifies Novel Regulators of Axon Pathfinding

Axon pathfinding is a key step in neural circuits formation. However, the transcriptional mechanisms regulating its progression remain poorly understood. The binary decision of crossing or avoiding the midline taken by some neuronal axons during development represents a robust model to investigate the mechanisms that control the selection of axonal trajectories. Here, to identify novel regulators of axon guidance, this work compares the transcriptome and chromatin occupancy profiles of two neuronal subpopulations, ipsilateral (iRGC) and contralateral retinal ganglion cells (cRGC), with similar functions but divergent axon trajectories. These analyses retrieved a number of genes encoding for proteins not previously implicated in axon pathfinding. In vivo functional experiments confirm the implication of some of these candidates in axonal navigation. Among the candidate genes, γ-synuclein is identified as essential for inducing midline crossing. Footprint and luciferase assays demonstrate that this small-sized protein is regulated by the transcription factor (TF) Pou4f1 in cRGCs. It is also shown that Lhx2/9 are specifically expressed in iRGCs and control a program that partially overlaps with that regulated by Zic2, previously described as essential for iRGC specification. Overall, the analyses identify dozens of new molecules potentially involved in axon guidance and reveal the regulatory logic behind the selection of axonal trajectories.

更新日期：2022-08-21

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南