摘要
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.
基金
STI2030-Major Projects(2022ZD0204900)
Natural Science Foundation of Shanghai(22ZR1466300,23ZR1413500)
National Natural Science Foundation of China(82401384,32271072)
Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)
Shanghai Sailing Program of the Shanghai Municipal Science and Technology Program(23YF1407500)
Shanghai Blue Cross Brain Hospital Co.,Ltd
Shanghai Tongji University Education Development Foundation
Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)
Zhangjiang(ZJ)Lab。
