RRC ID 87386
著者 Liu TT, Li HY, Gu SY, Sun L, Zhang RW, Zu JL, Zhang Y, Yu SG, Zheng XD, Yin JA, Chen Q, He J, Xu B, Du JL.
タイトル NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish.
ジャーナル Nat Commun
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.
巻・号 16(1)
ページ 10856
公開日 2025-12-9
DOI 10.1038/s41467-025-66543-9
PII 10.1038/s41467-025-66543-9
PMID 41365899
PMC PMC12689849
MeSH 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
IF 12.121
リソース情報
ゼブラフィッシュ UAS:GFP Tg(HuC:cameleon2.1)