PUBLICATION
NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish
- Authors
- Liu, T.T., Li, H.Y., Gu, S.Y., Sun, L., Zhang, R.W., Zu, J.L., Zhang, Y., Yu, S.G., Zheng, X.D., Yin, J.A., Chen, Q., He, J., Xu, B., Du, J.L.
- ID
- ZDB-PUB-251210-10
- Date
- 2025
- Source
- Nature communications 16: 1085610856 (Journal)
- Registered Authors
- Du, Jiu Lin, He, Jie, Li, Hong-Yu
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Brain*/blood supply
- Brain*/embryology
- Brain*/metabolism
- Calcium/metabolism
- Cell Communication
- Endothelial Cells*/metabolism
- Gene Expression Regulation, Developmental
- Neovascularization, Physiologic*
- Neurons*/metabolism
- Receptors, N-Methyl-D-Aspartate*/genetics
- Receptors, N-Methyl-D-Aspartate*/metabolism
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41365899 Full text @ Nat. Commun.
Citation
Liu, T.T., Li, H.Y., Gu, S.Y., Sun, L., Zhang, R.W., Zu, J.L., Zhang, Y., Yu, S.G., Zheng, X.D., Yin, J.A., Chen, Q., He, J., Xu, B., Du, J.L. (2025) NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish. Nature communications. 16:1085610856.
Abstract
N-methyl-D-aspartate receptors (NMDARs) are a major class of glutamate receptors crucial for neural development and function. Here, we report that NMDARs expressed on neurons regulate brain vascular development via neurovascular communication. Dysfunction of neuronal NMDARs impairs the formation of the zebrafish brain vasculature and abrogates the neural activity-induced enhancement of the brain vascular development. These defects are attributed to the reduced growth of vascular endothelial tip cells (ETCs) situating at the leading edge of brain angiogenic sprouts. At the molecular level, NMDAR dysfunction down-regulates neuronal expression of vascular endothelial growth factor and subsequent global Ca2+ activities of ETCs, thereby impairing ETC growth. Thus, our study uncovers an important role of NMDARs in brain vascular development, expanding the functional repertoire of NMDARs and the mechanistic understanding of the interplay between nervous and vascular systems during development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping