Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity

Kyrousi, Christina; O'Neill, Adam C.; Brazovskaja, Agnieska; He, Zhisong; Kielkowski, Pavel; Coquand, Laure; Di Giaimo, Rossella; D' Andrea, Pierpaolo; Belka, Alexander; Echeverry, Andrea Forero; Mei, Davide; Lenge, Matteo; Cruceanu, Cristiana; Buchsbaum, Isabel Y.; Khattak, Shahryar; Fabien, Guimiot; Binder, Elisabeth; Elmslie, Frances; Guerrini, Renzo; Baffet, Alexandre D.; Sieber, Stephan A.; Treutlein, Barbara; Robertson, Stephen P. und Cappello, Silvia (2021): Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity. In: Nature Communications, Bd. 12, Nr. 1, 6298

Abstract

Basal progenitors are enriched in gyrencephalic species like humans contributing to neuronal expansion. Here the authors show that LGALS3BP de novo variants are related to reduced cortical complexity and area in humans and that LGALS3BP regulates neural progenitor position in organoids, human fetal tissue and mice. 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• Sprache: Englisch