Regulation of angiogenesis in zebrafish
Generation of a functional vascular system is a highly regulated complex process, which is disturbed in a large number of human diseases, like cancer, ischemia or diabetes.
We use zebrafisch mutants identified from a genetic screen to identify new genes regulating angiogenesis. Additionally we are identifying the downstream pathway components important for endothelial cell differentiation and migration by microarray and deep sequencing approaches, and consecutive in vivo analysis.
- To understand, visualize and manipulate the endothelial cell migration in zebrafish embryos we are using and generating a number of transgenic zebrafish lines enabling us to follow (or influence) individual endothelial cells in the living animal (e.g. using confocal time laps imaging)
- To manipulate signaling pathways in the embryo we are using pharmacological inhibition or stimulation, transgenic overexpression, morpholino based gene-knockdown and Talen-mediated gene mutation.
- Of the signaling pathways regulating angiogenesis, we are currently focussing on the role of canonical Wnt signaling. We are analyzing its influence on endothelial cell specification, migration and blood-brain barrier formation in the embryo as well as in blood-brain barrier function in the adult fish.