Tao Yun-Chao, Zhao Li, Zhang Qiong, Liu Xi-Yue, Liu Wei-Tang, Li Ze-Xuan, Hu Ling, Zhang Lei, Chen Jia-Yin, Ding Yu-Qiang, Song Ning-Ning
State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
Laboratory Animal Center, Fudan University, Shanghai, 200032, China.
Neurosci Bull. 2025 Sep 8. doi: 10.1007/s12264-025-01496-z.
Nr4a2 (Nurr1) is well known to be vital for midbrain dopaminergic neurons. Recent single-cell RNA analyses reveal that Nr4a2 is expressed in lateral cerebral regions, within neurons named L4/L5/L6 IT Car3. These neurons have attracted intense attention for the molecular mechanisms underlying their development and functions. We classified Car3 neurons into neocortical (Ncx-Car3), claustral (CLA-Car3), and dorsal endopiriform nucleus (dEn-Car3) subpopulations, focusing on the characterization of Ncx-Car3 neurons. These neurons exhibit distinct birthdates and migratory morphologies compared to CLA- and dEn-Car3 neurons, but share a common transcriptomic profile when Nr4a2 is deleted at the embryonic stage or in adulthood. Notably, Nr4a2 misexpression ectopically induces Car3-enriched genes in vivo. Mice lacking Nr4a2 in Car3 ensembles during the embryonic stage or in adulthood display hyperactivity and reduced anxiety-like behaviors. Therefore, our results demonstrate that Nr4a2 is a key factor in regulating the development and functional maintenance of the forebrain Car3 neurons.
众所周知，Nr4a2（Nurr1）对中脑多巴胺能神经元至关重要。最近的单细胞RNA分析表明，Nr4a2在大脑外侧区域名为L4/L5/L6 IT Car3的神经元中表达。这些神经元因其发育和功能的分子机制而备受关注。我们将Car3神经元分为新皮质（Ncx-Car3）、屏状核（CLA-Car3）和背侧内梨状核（dEn-Car3）亚群，重点研究Ncx-Car3神经元的特征。与CLA-和dEn-Car3神经元相比，这些神经元表现出不同的出生日期和迁移形态，但在胚胎期或成年期缺失Nr4a2时，它们具有共同的转录组特征。值得注意的是，Nr4a2的异位表达在体内可异位诱导富含Car3的基因。在胚胎期或成年期Car3群体中缺乏Nr4a2的小鼠表现出多动和焦虑样行为减少。因此，我们的结果表明，Nr4a2是调节前脑Car3神经元发育和功能维持的关键因素。
