Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions
11 affiliations
- 1Centre de Recherche, CHU Sainte Justine, Montréal, QC, Canada
- 2Département de Pharmacologie et de Physiologie, Université de Montréal, Montréal, QC, Canada
- 3Laboratoire d'Imagerie optique et Moléculaire, Polytechnique Montréal, Montréal, QC, Canada
- 4Centre de Recherche, Montréal Heart Institute, Montréal, QC, Canada
- 5Metabolomics platform, Montréal Heart Institute, Montréal, QC, Canada
- 6Département de nutrition, Université de Montréal, Montréal, QC, Canada
- 7Département de Pédiatrie, Université de Montréal, Montréal, QC, Canada
- 8Centre de Recherche, CHU Sainte Justine, Montréal, QC, Canada. [email protected]
- 9Département d'Ophtalmologie, Université de Montréal, Montréal, QC, Canada. [email protected]
- 10Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC, Canada. [email protected]
- 11Département de Pharmacologie et de Physiologie, Université de Montréal, Montréal, QC, Canada. [email protected]
Abstract
Neurovascular interactions (NVIs) are critical in establishing vascular patterning, barrier function, and in regulating cerebral blood flow, thereby maintaining neuronal homeostasis and brain health. While developmental programs and neuronal activity play a central role in cerebral cortex angiogenesis during a critical postnatal period, whether cellular heterogeneity causes region-specific angiogenic regulation remains unknown. Here, we combine spatial and endothelial single-cell RNAseq (scRNAseq) transcriptomic analysis to establish a molecular atlas of developing brain regions and a comprehensive list of spatiotemporal-specific NVIs. We find that the thalamic area has a higher vascular density than the other brain regions and our atlas identifies transforming growth factor β ( Tgfβ ) and Vegfc ligands enrichment in this area during a critical postnatal period. Neonatal endothelial Tgfβr1 deletion ( Tgfβr1iEKO ) induces vascular malformations and hemorrhages, primarily in the thalamic area. Mechanistically, we show that loss of endothelial TGFβ signaling increases VEGFC-induced AKT/mTOR signaling in vitro and in vivo , and that mTOR inhibitor Rapamycin efficiently inhibits intracerebral bleeding and vascular defects in Tgfβr1iEKO mice. Altogether, our data suggest that spatiotemporal-specific NVIs control brain vascular heterogeneity, which extends our knowledge of region-specific cerebrovascular development and will benefit our understanding of neurovascular disorders.
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BibTeX
@article{bizou2026mapping,
title = {{Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions}},
author = {Mathilde Bizou and Elise Drapé and Gaël Cagnone and Joel P. Howard and Frans Irgolitsch and Séverine Leclerc and Mei Xi Chen and Blanche Boisseau and Isabelle Robillard Frayne and Matthieu Ruiz and Frédéric Lesage and Jean‐Sébastien Joyal and Grégor Andelfinger and Alexandre Dubrac},
journal = {Nature Communications},
year = {2026},
month = may,
doi = {10.1038/s41467-026-73373-w},
url = {https://doi.org/10.1038/s41467-026-73373-w},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions
AU - Mathilde Bizou
AU - Elise Drapé
AU - Gaël Cagnone
AU - Joel P. Howard
AU - Frans Irgolitsch
AU - Séverine Leclerc
AU - Mei Xi Chen
AU - Blanche Boisseau
AU - Isabelle Robillard Frayne
AU - Matthieu Ruiz
AU - Frédéric Lesage
AU - Jean‐Sébastien Joyal
AU - Grégor Andelfinger
AU - Alexandre Dubrac
PY - 2026
DA - 2026/05/22
JO - Nature Communications
DO - 10.1038/s41467-026-73373-w
UR - https://doi.org/10.1038/s41467-026-73373-w
AB - Neurovascular interactions (NVIs) are critical in establishing vascular patterning, barrier function, and in regulating cerebral blood flow, thereby maintaining neuronal homeostasis and brain health. While developmental programs and neuronal activity play a central role in cerebral cortex angiogenesis during a critical postnatal period, whether cellular heterogeneity causes region-specific angiogenic regulation remains unknown. Here, we combine spatial and endothelial single-cell RNAseq (scRNAseq) transcriptomic analysis to establish a molecular atlas of developing brain regions and a comprehensive list of spatiotemporal-specific NVIs. We find that the thalamic area has a higher vascular density than the other brain regions and our atlas identifies transforming growth factor β ( Tgfβ ) and Vegfc ligands enrichment in this area during a critical postnatal period. Neonatal endothelial Tgfβr1 deletion ( Tgfβr1iEKO ) induces vascular malformations and hemorrhages, primarily in the thalamic area. Mechanistically, we show that loss of endothelial TGFβ signaling increases VEGFC-induced AKT/mTOR signaling in vitro and in vivo , and that mTOR inhibitor Rapamycin efficiently inhibits intracerebral bleeding and vascular defects in Tgfβr1iEKO mice. Altogether, our data suggest that spatiotemporal-specific NVIs control brain vascular heterogeneity, which extends our knowledge of region-specific cerebrovascular development and will benefit our understanding of neurovascular disorders.
SN - 2041-1723
ER -