TY - JOUR
T1 - GPR126 is a specifier of blood-brain barrier formation in the mouse central nervous system
AU - Kakogiannos, Nikolaos
AU - Scalise, Anna Agata
AU - Martini, Emanuele
AU - Maderna, Claudio
AU - Benvenuto, Andrea Francesco
AU - D'Antonio, Michele
AU - Carmignani, Laura
AU - Magni, Serena
AU - Gullotta, Giorgia Serena
AU - Lampugnani, Maria Grazia
AU - Iannelli, Fabio
AU - Beznoussenko, Galina V.
AU - Mironov, Alexander A.
AU - Cerutti, Camilla
AU - Bentley, Katie
AU - Philippides, Andrew
AU - Zanardi, Federica
AU - Bacigaluppi, Marco
AU - Sigismund, Sara
AU - Bassani, Claudia
AU - Farina, Cinthia
AU - Martino, Gianvito
AU - De Giovanni, Marco
AU - Dejana, Elisabetta
AU - Iannacone, Matteo
AU - Inverso, Donato
AU - Giannotta, Monica
N1 - Publisher Copyright:
Copyright: © 2024, Kakogiannos et al.
PY - 2024
Y1 - 2024
N2 - The blood-brain barrier (BBB) acquires unique properties to regulate neuronal function during development. The formation of the BBB, which occurs in tandem with angiogenesis, is directed by the Wnt/β-catenin signaling pathway. Yet the exact molecular interplay remains elusive. Our study reveals the G protein-coupled receptor GPR126 as a critical target of canonical Wnt signaling, essential for the development of the BBB's distinctive vascular characteristics and its functional integrity. Endothelial cell-specific deletion of the Gpr126 gene in mice induced aberrant vascular morphogenesis, resulting in disrupted BBB organization. Simultaneously, heightened transcytosis in vitro compromised barrier integrity, resulting in enhanced vascular permeability. Mechanistically, GPR126 enhanced endothelial cell migration, pivotal for angiogenesis, acting through an interaction between LRP1 and β1 integrin, thereby balancing the levels of β1 integrin activation and recycling. Overall, we identified GPR126 as a specifier of an organotypic vascular structure, which sustained angiogenesis and guaranteed the acquisition of the BBB properties during development.
AB - The blood-brain barrier (BBB) acquires unique properties to regulate neuronal function during development. The formation of the BBB, which occurs in tandem with angiogenesis, is directed by the Wnt/β-catenin signaling pathway. Yet the exact molecular interplay remains elusive. Our study reveals the G protein-coupled receptor GPR126 as a critical target of canonical Wnt signaling, essential for the development of the BBB's distinctive vascular characteristics and its functional integrity. Endothelial cell-specific deletion of the Gpr126 gene in mice induced aberrant vascular morphogenesis, resulting in disrupted BBB organization. Simultaneously, heightened transcytosis in vitro compromised barrier integrity, resulting in enhanced vascular permeability. Mechanistically, GPR126 enhanced endothelial cell migration, pivotal for angiogenesis, acting through an interaction between LRP1 and β1 integrin, thereby balancing the levels of β1 integrin activation and recycling. Overall, we identified GPR126 as a specifier of an organotypic vascular structure, which sustained angiogenesis and guaranteed the acquisition of the BBB properties during development.
UR - http://www.scopus.com/inward/record.url?scp=85200311015&partnerID=8YFLogxK
U2 - 10.1172/JCI165368
DO - 10.1172/JCI165368
M3 - Article
C2 - 39087467
AN - SCOPUS:85200311015
SN - 0021-9738
VL - 134
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 15
M1 - e165368
ER -