Author response: Endothelial cell-type-specific molecular requirements for angiogenesis drive fenestrated vessel development in the brain [peer_review]

Sweta Parab, Rachael E Quick, Ryota L Matsuoka
2020 unpublished
Vascular endothelial cells (vECs) in the brain exhibit structural and functional heterogeneity. Fenestrated, permeable brain vasculature mediates neuroendocrine function, bodyfluid regulation, and neural immune responses; however, its vascular formation remains poorly understood. Here, we show that specific combinations of vascular endothelial growth factors (Vegfs) are required to selectively drive fenestrated vessel formation in the zebrafish myelencephalic choroid plexus (mCP). We found that
more » ... mCP). We found that the combined, but not individual, loss of Vegfab, Vegfc, and Vegfd causes severely impaired mCP vascularization with little effect on neighboring non-fenestrated brain vessel formation, demonstrating fenestrated-vEC-specific angiogenic requirements. This Vegfs-mediated vessel-selective patterning also involves Ccbe1. Expression analyses, cell-type-specific ablation, and paracrine activity-deficient vegfc mutant characterization suggest that vEC-autonomous Vegfc and meningeal fibroblast-derived Vegfab and Vegfd are critical for mCP vascularization. These results define molecular cues and cell types critical for directing fenestrated CP vascularization and indicate that vECs' distinct molecular requirements for angiogenesis underlie brain vessel heterogeneity. Parab et al. eLife 2021;10:e64295. DOI: https://doi.org/10.7554/eLife.64295 1 of 33 RESEARCH ARTICLE Parab et al. eLife 2021;10:e64295.
doi:10.7554/elife.64295.sa2 fatcat:y7klluxmg5ebpamng3t7hi25u4