TY - JOUR
T1 - Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity
AU - Kyrousi, Christina
AU - O’Neill, Adam C.
AU - Brazovskaja, Agnieska
AU - He, Zhisong
AU - Kielkowski, Pavel
AU - Coquand, Laure
AU - Di Giaimo, Rossella
AU - D’ Andrea, Pierpaolo
AU - Belka, Alexander
AU - Forero Echeverry, Andrea
AU - Mei, Davide
AU - Lenge, Matteo
AU - Cruceanu, Cristiana
AU - Buchsbaum, Isabel Y.
AU - Khattak, Shahryar
AU - Fabien, Guimiot
AU - Binder, Elisabeth
AU - Elmslie, Frances
AU - Guerrini, Renzo
AU - Baffet, Alexandre D.
AU - Sieber, Stephan A.
AU - Treutlein, Barbara
AU - Robertson, Stephen P.
AU - Cappello, Silvia
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85118465418&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-26447-w
DO - 10.1038/s41467-021-26447-w
M3 - Article
C2 - 34728600
AN - SCOPUS:85118465418
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6298
ER -
