LHX2 regulates dendritic morphogenesis in layer II/III neurons of the neocortex

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-02 DOI:10.1126/sciadv.ado1384

Mahima Bose, Sreenath Ravindran, Sanjna Kumari, Achintya Srivastava, Archana Iyer, Binita Vedak, Ishita Talwar, Rishikesh Narayanan, Shubha Tole

{"title":"LHX2 regulates dendritic morphogenesis in layer II/III neurons of the neocortex","authors":"Mahima Bose, Sreenath Ravindran, Sanjna Kumari, Achintya Srivastava, Archana Iyer, Binita Vedak, Ishita Talwar, Rishikesh Narayanan, Shubha Tole","doi":"10.1126/sciadv.ado1384","DOIUrl":null,"url":null,"abstract":"<div >In the mammalian neocortex, the two hemispheres communicate via the corpus callosum. We investigated mechanisms regulating dendritic arbors and spines of callosal neurons. The transcription factor LIM Homeodomain 2 (Lhx2), a key regulator of cortical development, is expressed in postmitotic layer II/III neurons and their progenitors. Loss of Lhx2 in either population caused similar but distinct phenotypes: reduced dendritic arbors, altered spine morphology, and changed electrophysiological properties. Morphometric defects were more severe when Lhx2 was disrupted in progenitors and were recapitulated by its specific loss in basal progenitors. Lhx2 loss in progenitors aberrantly up-regulated Neurog2 in postmitotic neurons, and Neurog2 knockdown partially rescued the phenotype. Loss of Lhx2 at either stage also up-regulated Wnt signaling pathway genes. The mutant phenotype was mimicked by constitutive activation of β-CATENIN in postmitotic neurons. Our findings reveal previously unidentified LHX2-dependent mechanisms of dendritic morphogenesis, highlighting its temporally dynamic and diverse roles in neocortical development.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 27","pages":""},"PeriodicalIF":12.5000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado1384","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/sciadv.ado1384","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

In the mammalian neocortex, the two hemispheres communicate via the corpus callosum. We investigated mechanisms regulating dendritic arbors and spines of callosal neurons. The transcription factor LIM Homeodomain 2 (Lhx2), a key regulator of cortical development, is expressed in postmitotic layer II/III neurons and their progenitors. Loss of Lhx2 in either population caused similar but distinct phenotypes: reduced dendritic arbors, altered spine morphology, and changed electrophysiological properties. Morphometric defects were more severe when Lhx2 was disrupted in progenitors and were recapitulated by its specific loss in basal progenitors. Lhx2 loss in progenitors aberrantly up-regulated Neurog2 in postmitotic neurons, and Neurog2 knockdown partially rescued the phenotype. Loss of Lhx2 at either stage also up-regulated Wnt signaling pathway genes. The mutant phenotype was mimicked by constitutive activation of β-CATENIN in postmitotic neurons. Our findings reveal previously unidentified LHX2-dependent mechanisms of dendritic morphogenesis, highlighting its temporally dynamic and diverse roles in neocortical development.

Abstract Image

查看原文本刊更多论文

LHX2调节新皮层II/III层神经元的树突形态发生

在哺乳动物的新皮层中，两个半球通过胼胝体进行交流。我们研究了调节胼胝体神经元树突和棘的机制。转录因子LIM同源结构域2 （Lhx2）是皮质发育的关键调节因子，在有丝分裂后II/III层神经元及其祖细胞中表达。Lhx2的缺失在两个种群中引起相似但不同的表型：树突乔木减少，脊柱形态改变，电生理特性改变。当Lhx2在祖细胞中被破坏时，形态测量缺陷更为严重，并且在基底祖细胞中被特异性丢失。祖细胞中Lhx2缺失异常上调有丝分裂后神经元中的Neurog2，而Neurog2敲低部分挽救了表型。Lhx2在两个阶段的缺失也上调了Wnt信号通路基因。突变表型通过有丝分裂后神经元中β-CATENIN的组成性激活来模拟。我们的研究结果揭示了以前未确定的lhx2依赖性树突形态发生机制，突出了其在新皮层发育中的时间动态和多样化作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.