Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity.pdf (27.04 MB)
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Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity

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posted on 16.11.2022, 17:54 authored by Christina Kyrousi, Adam C O'Neill, Agnieska Brazovskaja, Zhisong He, Pavel Kielkowski, Laure Coquand, Rossella Di Giaimo, Pierpaolo D' Andrea, Alexander Belka, Andrea Forero Echeverry, Davide Mei, Matteo Lenge, Cristiana Cruceanu, Isabel Y Buchsbaum, Shahryar Khattak, Guimiot Fabien, Elisabeth Binder, Frances Elmslie, Renzo Guerrini, Alexandre D Baffet, Stephan A Sieber, Barbara Treutlein, Stephen P Robertson, Silvia Cappello

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. 

Funding

Projekt DEAL

History

Comments

The original article is available at https://www.nature.com/

Published Citation

Kyrousi C. et al. Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity. Nat Commun. 2021;12(1):6298.

Publication Date

2 November 2021

PubMed ID

34728600

Department/Unit

  • RCSI Bahrain

Publisher

Nature Pub. Group

Version

  • Published Version (Version of Record)