Regulatory heterogeneity of Vegf- and Wnt7-dependent angiogenesis drives phenotypic diversity of brain vasculature

Phenotypic diversity of brain vasculature is important for brain region-specific neural function, but how this diversity emerges remains unclear. Here we show a core angiogenic mechanism critical for fenestrated brain vessel development via a comparative analysis of the choroid plexuses (CPs) and circumventricular organs (CVOs) in zebrafish, demonstrating vessel-type-selective vascularization mechanisms. We find that zebrafish deficient for Gpr124, Reck, or Wnt7aa exhibit severely-impaired brain angiogenesis without any apparent defect in fenestrated capillary formation in the CPs and CVOs. Conversely, various combinations of Vegfs direct heterogeneous regulation of 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. These comparative results reveal an unexpected, vital role for Vegfc in fenestrated vessel development across the brain and suggest that local and inter-tissue heterogeneity of angiogenic regulation promotes phenotypic diversity of brain vasculature. ### Competing Interest Statement The authors have declared no competing interest.