biostudies-literatureUnknown16(1)Liu TTN-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 Nature communications10856https://www.ebi.ac.uk/biostudies/studies/S-EPMC12689849biostudies-literatureNMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish.PMC12689849Yin JAChen QDu JLYu SGLiu TTHe JGu SYLi HYZhang RWZu JLSun LZheng XDZhang YXu BfalseNMDA 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 Ca²⁺ activities of ETCs, thereby impairing ETC growth. Thus, our study uncovers 2025-01-01T00:00:00Z2025 Dec2026-07-15T11:14:44.3Z2026-07-04T03:10:07.57ZS-EPMC126898494136589910.1038/s41467-025-66543-9