Mapping the cellular expression patterns of vascular endothelial growth factor aa and bb genes and their receptors in the adult zebrafish brain during constitutive and regenerative neurogenesis

Abstract

The complex interplay between vascular signaling and neurogenesis in the adult brain remains a subject of intense research. By exploiting the unique advantages of the zebrafish model, in particular the persistent activity of neural stem cells (NSCs) and the remarkable ability to repair brain lesions, we investigated the links between NSCs and cerebral blood vessels. In this study, we first examined the gene expression profiles of vascular endothelial growth factors aa and bb (vegfaa and vegfbb), under physiological and regenerative conditions. Using fluorescence in situ hybridization coupled to immunostaining/histology techniques, we demonstrated the wide expression of vegfaa and vegfbb across the brain, and showed their expression in neurons, microglia, endothelial cells and NSCs. At 1 day post-lesion (dpl), both vegfaa and vegfbb appeared to be up-regulated in neurons and microglia. When we looked at their receptors, we also found a high expression throughout the brain. We showed that vegfr are mainly expressed in neurons, microglia and endothelial cells. Interestingly, vegfr transcripts appeared to be expressed at lower levels in NSCs (mainly vegfr1, vegfr2 and vegfr3). However, Vegfr3 and Vegfr4 immunostainings confirmed their significant expression in these neurogenic cells. These data suggest a possible role of Vegf signaling in neurogenesis. After brain lesion (1 dpl), vegfr gene expression did not appear to be modulated but vegfr were expressed in proliferative cells within the injured parenchyma. Taken together, our results provide a first overview of Vegf/Vegfr signaling in the brain and suggest key roles of Vegf in neurogenesis and regenerative processes.