Galectin-3 induces neurodevelopmental apical-basal polarity and regulates gyrification

IF 12.5 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Luana Campos Soares, Ning Huang, Hana Bernhardova, Viviana Macarelli, Marva Chan, Lara Nikel, Sara Bandiera, Dongnan Yan, Dhanu Gupta, Elisa M. Cruz, Talia Vasaturo-Kolodner, James M. Hillis, Matthew Wood, Mootaz Salman, Zoltán Molnár, Eric O’Neill, Francis G. Szele
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引用次数: 0

Abstract

Apical-basal polarity (ABP) establishment and maintenance is necessary for proper brain development, yet how it is controlled is unclear. Galectin-3 (Gal-3) has been previously implicated in ABP of epithelial cells, and, here, we find that it is apically expressed in human embryonic stem cells (hESCs) during neural induction. Gal-3 blockade disrupts ABP and alters the distribution of junctional proteins in hESC-derived neural rosettes and is rescued by addition of recombinant Gal-3. Transcriptomics analysis shows that blocking Gal-3 regulates expression of genes responsible for nervous system development and cell junction assembly, among others. Last, Gal-3 blockade during embryonic development in vivo reduces horizontal cell divisions, disturbs cortical layering of neural progenitors, and induces gyrification. These data uncover a regulatory mechanism for ABP in the brain and warrant caution in modulating Gal-3 during pregnancy.

Abstract Image

半乳糖凝集素-3诱导神经发育的顶基极性并调节旋回
顶基极性(ABP)的建立和维持是大脑正常发育所必需的,但其控制机制尚不清楚。半乳糖凝集素-3 (Gal-3)先前与上皮细胞的ABP有关,在这里,我们发现它在神经诱导过程中在人胚胎干细胞(hESCs)中顶端表达。Gal-3阻断破坏ABP并改变hesc来源的神经花环中连接蛋白的分布,并通过添加重组Gal-3来挽救。转录组学分析表明,阻断Gal-3可调节神经系统发育和细胞连接组装等相关基因的表达。最后,体内胚胎发育过程中阻断Gal-3可减少水平细胞分裂,扰乱神经祖细胞皮层分层,并诱导旋回。这些数据揭示了ABP在大脑中的调节机制,并在怀孕期间调节Gal-3时需要谨慎。
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来源期刊
Science Advances
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.
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