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Lhx2 在小鼠新皮质皮质上层中皮质出生后神经元的迁移和轴突投射中的作用。

A role of Lhx2 in the migration and axonal projection of cortical postmitotic neurons in the cortical upper layer of the mouse neocortex.

机构信息

Department of Biochemistry, Chungbuk National University, Cheongju, 28644, Republic of Korea.

Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2024 Nov 19;734:150780. doi: 10.1016/j.bbrc.2024.150780. Epub 2024 Oct 1.

DOI:10.1016/j.bbrc.2024.150780
PMID:39362030
Abstract

The transcription factor LHX2 contains a LIM domain and plays an important role in the development of the vertebrate nervous system. Although much research has been conducted on the function of Lhx2 during cerebral development, its role in postmitotic neuron differentiation in the cerebral cortex remains unknown. Therefore, this study was conducted to determine the function of Lhx2 in dynamic and elaborate developmental processes, including neurogenesis. We first created and confirmed an Lhx2-BAC Gfp transgenic model to three-dimensionally confirm the spatiotemporal expression pattern of Lhx2 during brain development. On this basis, we used the bilateral in utero electroporation technique to express the dominant-negative form of LHX2. LHX2 was confirmed to be important for the migration and callosal projection of postmitotic neurons that form the upper layer of the cerebral cortex during neurogenesis. Additionally, transcriptome analysis confirmed that LHX2 affected the genes involved in neuronal migration and axonal projection. We demonstrated that Lhx2 is important for postmitotic neurons in the cerebral cortex, which migrate to normal positions and extend nerve axons. Taken together, our findings can provide important clues to understanding the relationship between human Lhx2 gene mutations and brain developmental diseases.

摘要

转录因子 LHX2 包含 LIM 结构域,在脊椎动物神经系统的发育中发挥着重要作用。尽管在大脑发育过程中对 Lhx2 的功能进行了大量研究,但它在大脑皮层的有丝分裂后神经元分化中的作用仍不清楚。因此,本研究旨在确定 Lhx2 在包括神经发生在内的动态和精细发育过程中的功能。我们首先创建并证实了 Lhx2-BAC Gfp 转基因模型,以三维方式确认 Lhx2 在大脑发育过程中的时空表达模式。在此基础上,我们使用双侧子宫内电穿孔技术表达显性负形式的 LHX2。LHX2 对于神经发生过程中形成大脑皮层上层的有丝分裂后神经元的迁移和胼胝体投射是重要的。此外,转录组分析证实 LHX2 影响参与神经元迁移和轴突投射的基因。我们证明 Lhx2 对于大脑皮层中的有丝分裂后神经元是重要的,这些神经元迁移到正常位置并延伸神经轴突。总之,我们的发现可以为理解人类 Lhx2 基因突变与大脑发育疾病之间的关系提供重要线索。

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