| RRC ID |
87386
|
| Author |
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.
|
| Title |
NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk in zebrafish.
|
| Journal |
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.
|
| Volume |
16(1)
|
| Pages |
10856
|
| Published |
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
|
| Resource |
| Zebrafish |
UAS:GFP
Tg(HuC:cameleon2.1) |
