What are the cellular and molecular mechanisms that govern development and maintenance of the BBB?
We are interested in identifying key signaling pathways that regulate formation of the BBB in order to repair BBB function in CNS diseases in which the barrier breaks down.
We have found that the Wnt/beta-catenin pathway plays an important role in regulating both CNS angiogenesis and some properties of the barrier. We have identified a novel inhibitor of this pathway named Apcdd1 that is expressed in CNS endothelial cells when they acquire their barrier properties during development. We are currently investigating the roles of Apcdd1 in CNS angiogenesis and blood-brain barrier development.
We are also interested in understanding how tight junctions between endothelial cells in the CNS develop and mature during BBB formation. We have developed proteomic discovery platforms for: a) identifying novel junctional proteins important for barrier development and function; and b) potential structural modifications of tight junction proteins that underlie CNS diseases exhibiting reduced barrier function.
- Cottarelli A, Corada M, Beznoussenko GV, Mironov AA, Globisch MA, Biswas S, Huang H, Dimberg A, Magnusson PU, Agalliu D, Lampugnani MG, Dejana E. (2020) Fgfbp1 promotes blood-brain barrier development by regulating collagen IV deposition and maintaining Wnt/β-catenin signaling. Development Aug 24;147(16):dev185140
- Biswas S, Cottarelli A, Agalliu D. (2020) Neuronal and glial regulation of CNS angiogenesis and barriergenesis.