| First Author | O'Brown NM | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 17 | Pages | 1534-1547.e6 |
| PubMed ID | 37437574 | Mgi Jnum | J:340367 |
| Mgi Id | MGI:7528590 | Doi | 10.1016/j.devcel.2023.06.005 |
| Citation | O'Brown NM, et al. (2023) The secreted neuronal signal Spock1 promotes blood-brain barrier development. Dev Cell 58(17):1534-1547.e6 |
| abstractText | 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. |
