Mural cells protect the adult brain from hemorrhage but do not control the blood-brain barrier in developing zebrafish.
OF, B., A, U.G., S, D., W, W., S, P., MC, R.G., YW, L., J, R., A, L., & RG, P. (2026). Mural cells protect the adult brain from hemorrhage but do not control the blood-brain barrier in developing zebrafish.. eLife. https://doi.org/10.7554/eLife.104061
OF B, A UG, S D, W W, S P, MC RG, et al. Mural cells protect the adult brain from hemorrhage but do not control the blood-brain barrier in developing zebrafish.. eLife. 2026; doi: 10.7554/eLife.104061
OF B, A UG, S D, et al. Mural cells protect the adult brain from hemorrhage but do not control the blood-brain barrier in developing zebrafish.[J]. eLife. 2026. DOI: 10.7554/eLife.104061.
@article{of2026,
author = {Baltaci OF and Usseglio Gaudi A and Dudczig S and Wang W and Paterson S and Rondon-Galeano MC and Lim YW and Rae J and Lagendijk A and Parton RG},
title = {Mural cells protect the adult brain from hemorrhage but do not control the blood-brain barrier in developing zebrafish.},
journal = {eLife},
year = {2026},
doi = {10.7554/eLife.104061},
note = {PMID: 42223470},
}
TY - JOUR AU - Baltaci OF AU - Usseglio Gaudi A AU - Dudczig S AU - Wang W AU - Paterson S AU - Rondon-Galeano MC AU - Lim YW AU - Rae J AU - Lagendijk A AU - Parton RG TI - Mural cells protect the adult brain from hemorrhage but do not control the blood-brain barrier in developing zebrafish. T2 - eLife PY - 2026 DO - 10.7554/eLife.104061 AN - PMID:42223470 ER -
The blood-brain barrier (BBB) protects the brain from circulating metabolites and plays central roles in neurological diseases. Endothelial cells (ECs) of the BBB are enwrapped by mural cells including pericytes and vascular smooth muscle cells (vSMCs) that regulate angiogenesis, vessel stability and barrier function. To explore mural cell control of the BBB, we investigated neurovascular phenotypes in zebrafish pdgfrb mutants that lack brain pericytes and vSMCs. As expected, mutants showed an altered cerebrovascular network with mispatterned capillaries. Unexpectedly, mutants displayed no BBB leakage at larval stages of development. This suggests that pericytes and vSMCs are not essential for normal BBB function in developing zebrafish. Instead, we observed juvenile and adult BBB disruption occurring at 'hotspot' focal hemorrhages at large vessel aneurysms. ECs at leakage hotspots showed induction of caveolae on abluminal surfaces and structural defects including basement membrane thickening and disruption. Our work suggests that capillary pericytes primarily regulate cerebrovascular patterning in development and vSMCs of major arteries protect from hemorrhage and BBB breakdown in older zebrafish. The fact that young zebrafish have a functional BBB in the absence of mural cells calls for renewed interrogation of mural cell control of the BBB throughout vertebrate evolution.