ABSTRACT
Fenestrated and blood-brain barrier (BBB)-forming endothelia constitute major brain capillaries that mediate blood-brain communications crucial for brain homeostasis. How these capillary types emerge in a brain region-specific manner remains unknown. Here we performed a comparative analysis of the zebrafish choroid plexuses (CPs) and circumventricular organs (CVOs), and show common angiogenic mechanisms for fenestrated brain capillary development. We found that zebrafish deficient for Gpr124, Reck, or Wnt7aa exhibit severely-impaired BBB angiogenesis without apparent defects in fenestrated capillary formation in the CPs and CVOs, demonstrating vessel-type-selective vascularization mechanisms. Conversely, simultaneous losses of various Vegf combinations revealed remarkable heterogeneity of endothelial requirements for Vegfs-dependent angiogenesis within and across these organs. Expression analysis suggests that endothelial cells and non-neuronal cell types uniquely present in the CPs and CVOs are major sources of Vegfs. Comparative analysis further uncovered unexpected, significant interplay of Vegfc/d and Vegfa in fenestrated vessel formation across the brain. These results identified brain-region-specific presentations and interplay of Vegfs underlying fenestrated capillary development.
TEASER Identification of novel and complex molecular interplay critical for directing permeable vascular formation across the brain
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
A manuscript has been updated.
Abbreviations
- ACeV
- Anterior cerebral vein
- BBB
- Blood–brain barrier
- CNS
- Central nervous system
- CPs
- Choroid plexuses
- CrDI
- Cranial division of the internal carotid artery
- CVOs
- Circumventricular organs
- CVP
- Choroidal vascular plexus
- Cyp26
- Cytochrome P450 family 26 enzymes
- DLV
- Dorsal longitudinal vein
- Glut1b
- Glucose transporter 1b
- HyA
- Hypophyseal artery
- Hy loop
- Hypophyseal loop
- HyV
- Hypophyseal veins
- MCeV
- Middle cerebral vein
- MsV
- Mesencephalic vein
- NH
- Neurohypophysis
- OA
- Optic artery
- OVLT
- Organum vasculosum of the lamina terminalis
- PCeV
- Posterior cerebral vein
- PG
- Pineal gland
- PGV
- Pineal gland vessel
- PLA
- Palatocerebral arteries
- PrA
- Prosencephalic artery
- Prop1
- Paired-Like Homeobox 1
- Plvap
- Plasmalemma vesicle-associated protein
- Pomca
- Proopiomelanocortin a
- vECs
- Vascular endothelial cells
- Vegfs
- Vascular endothelial growth factors