PUBLICATION
The secreted neuronal signal spock1 promotes blood-brain barrier development
- Authors
- O'Brown, N.M., Patel, N.B., Hartmann, U., Klein, A.M., Gu, C., Megason, S.G.
- ID
- ZDB-PUB-230713-39
- Date
- 2023
- Source
- Developmental Cell 58(17): 1534-1547.e6 (Journal)
- Registered Authors
- Megason, Sean, O'Brown, Natasha
- Keywords
- blood vessel, blood-brain barrier, development, genetics, leakage, zebrafish
- Datasets
- GEO:GSE230236
- MeSH Terms
-
- Animals
- Biological Transport
- Blood-Brain Barrier*/metabolism
- Brain
- Endothelium/metabolism
- Mice
- Proteoglycans*/metabolism
- Zebrafish*
- PubMed
- 37437574 Full text @ Dev. Cell
Citation
O'Brown, N.M., Patel, N.B., Hartmann, U., Klein, A.M., Gu, C., Megason, S.G. (2023) The secreted neuronal signal spock1 promotes blood-brain barrier development. Developmental Cell. 58(17):1534-1547.e6.
Abstract
The blood-brain barrier (BBB) is a unique set of properties of the brain vasculature which severely restrict its permeability to proteins and small molecules. Classic chick-quail chimera studies have shown that these properties are not intrinsic to the brain vasculature but rather are induced by surrounding neural tissue. Here, we identify Spock1 as a candidate neuronal signal for regulating BBB permeability in zebrafish and mice. Mosaic genetic analysis shows that neuronally expressed Spock1 is cell non-autonomously required for a functional BBB. Leakage in spock1 mutants is associated with altered extracellular matrix (ECM), increased endothelial transcytosis, and altered pericyte-endothelial interactions. Furthermore, a single dose of recombinant SPOCK1 partially restores BBB function in spock1 mutants by quenching gelatinase activity and restoring vascular expression of BBB genes including mcamb. These analyses support a model in which neuronally secreted Spock1 initiates BBB properties by altering the ECM, thereby regulating pericyte-endothelial interactions and downstream vascular gene expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping