Differential regulated angiogenesis of fenestrated and blood-brain barrier blood vessels in the zebrafish brain

• Applicant: Professor Dr. Christian Helker
• Subject Area: Developmental Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 528068898

During embryonic development new blood vessels are formed in all organs of the body in a process called angiogenesis. Research in the last years highlighted distinct signaling pathways driving the formation of blood vessels in different organs. Moreover, organotypic vascular beds adapt to the needs of the surrounding tissues to carry out organ specific functions. Yet our understanding of these organ-specific angiogenic programs and endothelial cell (EC) signaling pathways lags behind other aspects of vascular biology. Heterogeneity amongst different blood vessels in different organs or within the same organ is critical to carry out local requirements of the surrounding tissues. This heterogeneity is probably best illustrated in the vasculature of the central nervous system (CNS), where endothelial cells form an active permeability filter called the blood-brain barrier (BBB). However, some vessels in the brain need to be permeable to ensure exchange of molecules and hormones. The capillaries in the choroid plexuses (CPs) do not develop a tight BBB but instead have permeable pores called fenestrae that facilitate exchange of fluids, nutrients, and hormones between the blood, the cerebrospinal fluid (CSF), and the brain. In the past, research on fenestrated blood vessel formation gained only little attention. It has, however, come into focus in recent years because of the involvement of fenestrated blood vessels in several neurological disorders. In this project we will decipher the cellular and molecular events that lead to the formation of fenestrated blood vessels. In summary, this project will provide new insights into the basic principles of fenestrated blood vessel formation and provide a better understanding of fenestrated blood vessels under physiological and pathophysiological conditions.

• DFG Programme: Research Grants