NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish

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 Ca<sup>2+</sup> 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.

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Publication Details

Journal
Nature Communications
Published
2025-12-09
DOI
https://doi.org/10.1038/s41467-025-66543-9
Citations
1
Primary Topic
Zebrafish Biomedical Research Applications
Type
article
Field-Weighted Citation Impact
1.15

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article

NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish

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1 citations
Nature Communications
Zebrafish Biomedical Research Applications
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article

NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish

Shuguang Yu, Jiang‐An Yin, Shanye Gu, Qi Chen, Jiulin Du, Hongyu Li, Yu Zhang, Tingting Liu, Le Sun, Rongwei Zhang, Bing Xu, Xiudan Zheng, J. Zu, Jie He
article en
1 citations

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 Ca<sup>2+</sup> 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.

Nature CommunicationsVol. 16(1)
Nantong University (CN), ShanghaiTech University (CN), Center for Excellence in Brain Science and Intelligence Technology (CN), University of Chinese Academy of Sciences (CN), Nanjing Medical University (CN)
National Natural Science Foundation of China, Chinese Academy of Sciences
Openalex Percentile: Top 17%
Zebrafish Biomedical Research Applications
1.15
DOIOpen Access PDFOpenAlex
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