Development & Maintenance of the BBB

What are the cellular and molecular mechanisms that govern development and maintenance of the BBB?

P10 wild-type retina flat-mount immunostained for CD31 (red; endothelial cell), Collagen IV (blue; basement membrane) and endogenous IgG (green)
Vasculature of the developing retina

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.

Related publications

Current projects

Cellular and molecular mechanisms of blood-retina barrier formation and maintenance