Max Planck Institute of Psychiatry, 80804, Munich, Germany.
First Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, Greece and University Mental Health, Neurosciences and Precision Medicine Research Institute "Costas Stefanis", Athens, Greece.
Nat Commun. 2021 Nov 2;12(1):6298. doi: 10.1038/s41467-021-26447-w.
Basal progenitors (BPs), including intermediate progenitors and basal radial glia, are generated from apical radial glia and are enriched in gyrencephalic species like humans, contributing to neuronal expansion. Shortly after generation, BPs delaminate towards the subventricular zone, where they further proliferate before differentiation. Gene expression alterations involved in BP delamination and function in humans are poorly understood. Here, we study the role of LGALS3BP, so far known as a cancer biomarker, which is a secreted protein enriched in human neural progenitors (NPCs). We show that individuals with LGALS3BP de novo variants exhibit altered local gyrification, sulcal depth, surface area and thickness in their cortex. Additionally, using cerebral organoids, human fetal tissues and mice, we show that LGALS3BP regulates the position of NPCs. Single-cell RNA-sequencing and proteomics reveal that LGALS3BP-mediated mechanisms involve the extracellular matrix in NPCs' anchoring and migration within the human brain. We propose that its temporal expression influences NPCs' delamination, corticogenesis and gyrification extrinsically.
基底祖细胞（BPs）包括中间祖细胞和基底放射状胶质细胞，由顶端放射状胶质细胞产生，在具有脑回的物种（如人类）中丰富存在，有助于神经元的扩增。在产生后不久，BPs 向侧脑室下区（SVZ）分离，在那里进一步增殖后再分化。目前对于与 BP 分离和功能相关的基因表达改变在人类中了解甚少。在这里，我们研究了 LGALS3BP 的作用，它之前被认为是一种癌症生物标志物，是一种在人类神经祖细胞（NPCs）中丰富表达的分泌蛋白。我们发现 LGALS3BP 从头变异的个体其皮质局部脑回、脑沟深度、表面积和厚度发生改变。此外，通过大脑类器官、人类胎儿组织和小鼠，我们表明 LGALS3BP 调节 NPCs 的位置。单细胞 RNA 测序和蛋白质组学揭示了 LGALS3BP 介导的机制涉及 NPCs 中细胞外基质的锚定和在人脑内的迁移。我们提出，其时空表达从外部影响 NPCs 的分离、皮质发生和脑回形成。
