The transcription factor LHX2 suppresses astrocyte proliferation in the postnatal mammalian cerebral cortex.

IF 3.7 2区生物学 Q1 DEVELOPMENTAL BIOLOGY

Development Pub Date : 2025-10-15 Epub Date: 2025-06-02 DOI:10.1242/dev.204358

Archana Iyer, Reanne Fronteiro, Prachi Bhatia, Sanjna Kumari, Amrita Singh, Jiafeng Zhou, Riccardo Bocchi, Rishikesh Narayanan, Shubha Tole

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引用次数: 0

Abstract

In the developing cerebral cortex, astrocytes arise from progenitors in the ventricular and subventricular zones (V-SVZ), and also from local proliferation within the parenchyma. In the mouse neocortex, astrocytes that occupy upper layers (UL) versus deep layers (DL) are known to be distinct populations in terms of molecular and morphological features. The transcription factor LHX2 is expressed both in V-SVZ gliogenic progenitors and in differentiated astrocytes throughout development and into adulthood. Here, we show that loss of Lhx2 at birth results in an increased astrocyte proliferation in the UL but not the DL of the cortex in the first postnatal week. Consistent with this, transcriptomic signatures of UL astrocytes increase. By 3 months, Lhx2 mutant astrocytes display upregulation of GFAP, and transcriptomic signatures associated with 'reactive' astrocytes, in the absence of injury. These results demonstrate a role for Lhx2 in regulating proliferation and molecular features of cortical astrocytes.

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转录因子LHX2抑制出生后哺乳动物大脑皮层星形胶质细胞增殖。

在发育中的大脑皮层中，星形胶质细胞来自于脑室和脑室下区（V-SVZ）的祖细胞，也来自于实质内的局部增殖。在小鼠新皮层中，占据上层和深层（UL/DL）的星形胶质细胞在分子和形态特征方面是不同的群体。转录因子LHX2在V-SVZ胶质源性祖细胞和分化的星形胶质细胞中表达，贯穿发育直至成年。本研究表明，出生时Lhx2的缺失导致出生后第一周内UL中星形胶质细胞增殖增加，但皮质DL没有增加。与此一致，UL星形胶质细胞的转录组特征增加。到3个月时，Lhx2突变的星形胶质细胞在没有损伤的情况下表现出GFAP的上调，以及与“反应性”星形胶质细胞相关的转录组特征。这些结果表明Lhx2在调节皮质星形胶质细胞的增殖和分子特征方面具有新的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Development 生物-发育生物学

CiteScore

6.70

自引率

4.30%

发文量

433

审稿时长

3 months

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