Blood-tissue barriers protect the central nervous system and represent the major interfaces between the central nervous system and peripheral circulation. Damage to the barriers leads to long-term neurological toxicity in the development of many neurological diseases. Barriers are found in the brain endothelium, the choroid plexus epithelium, and the arachnoid epithelium. Drug exposure to the CNS is partially dependent on the physical barrier presented by the blood-brain and blood-CSF barrier and the affinity of the substrate for specific transport systems located at both of these interfaces. The choroid plexus epithelium, together with the arachnoid epithelium and the circumventricular organs collectively constitute the blood-CSF barrier. The choroid plexus is involved in the production and secretion of CSF. Our understanding of choroid plexus developmental biology is extremely limited. The proposed studies aim at exploring the molecular and cellular mechanisms underlying the formation of the choroid plexus. More specifically, using a combination of molecular, cellular and embryological approaches, morphogenesis and maturation of the choroid plexus and the mechanisms that guide its formation as well as the establishment of its barrier functions will be addressed in the context of the developing animal and in cell culture-based assays. Our general aim is to provide a comprehensive characterization of the choroid plexus, the central element of the blood-CSF barrier and an important, yet overlooked structure in the brain, 1 that may be potentially explored as a target for drug and gene delivery strategies for the treatment of neurological diseases.
