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Nat Commun ; 12(1): 6298, 2021 11 02.
Article in English | MEDLINE | ID: mdl-34728600

ABSTRACT

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.


Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Cerebral Cortex/cytology , Extracellular Vesicles/metabolism , Induced Pluripotent Stem Cells/cytology , Neocortex/cytology , Neural Stem Cells/cytology , Neuroglia/metabolism , Animals , Cell Differentiation , Cerebral Cortex/metabolism , Female , Humans , Induced Pluripotent Stem Cells/metabolism , Lateral Ventricles/cytology , Lateral Ventricles/metabolism , Mice , Mice, Inbred C57BL , Models, Animal , Neocortex/metabolism , Neural Stem Cells/metabolism
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