Differential regulation of angiogenesis and blood-brain barrier formation in zebrafish

• Applicant: Professorin Dr. Wiebke Herzog
• Subject Area: Developmental Neurobiology
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 269353708

The blood-brain barrier (BBB) is a permeability barrier established by the neurovascular unit to ensure brain tissue homeostasis and prevent toxic substances or pathogens from entering the central nervous system.Wnt signaling is active and required during different steps of brain vascularization and BBB formation. We have identified a novel regulatory function of Wnt signaling during brain angiogenesis and a novel crosstalk of the Wnt and Sphingosine 1 phosphate (S1P) signaling pathways. We therefore aim to understand the specific contributions of Wnt and S1P signaling to brain capillary angiogenesis, BBB formation and maintenance and especially the interaction of both pathways on a mechanistic level. For this work, we will exploit the advantages of the zebrafish as a model organism, especially its amenability to live imaging and fast transgenesis and genome editing in combination with using primary isolated mouse brain endothelial cells as a model for the developmental angiogenically active brain capillaries. We expect to gain novel insights into how the crosstalk between Wnt and S1P signaling regulates development and maintenance of the BBB.

• DFG Programme: Research Units
• Subproject of: FOR 2325: Interactions at the Neurovascular Interface