Endothelial cell type-specific molecular requirements for angiogenesis drive fenestrated vessel development in the brain

Vascular endothelial cells (vECs) in the brain exhibit structural and functional heterogeneity. Fenestrated, permeable brain vasculature mediates neuroendocrine function, body-fluid 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 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-deficientvegfc mutant characterization reveal that vEC-autonomous Vegfc and meningeal fibroblast-derived Vegfab and Vegfd are critical for mCP vascularization. These results define molecular cues and cell types essential for directing fenestrated CP vascularization and indicate that vECs' distinct molecular requirements for angiogenesis underlie brain vessel heterogeneity.
Source: eLife - Category: Biomedical Science Tags: Developmental Biology Source Type: research