"The choroid plexus: a key player in brain development and an unexplored brain barrier”

Host: Prof Liz Miller

Venue: MSI Small Lecture Theatre, SLS

Abstract

The choroid plexus (ChP) is a highly secretory tissue and an important signalling centre located in our brain. This tissue displays a number of important functions such as forming a protective epithelial barrier and secreting the cerebrospinal fluid (CSF). The CSF is important for the maintenance of physiological levels of nutrients in the brain, for the transport of signalling molecules and growth factors and for its protective role in the regulation of intracranial pressure. Most of the studies about the ChP have been conducted in rodents or 2D models, which don’t fully recapitulate the complexity of human ChP. To explore the role of the ChP-CSF system, we recently established a protocol to generate human ChP organoids using a combination of signalling molecules that are physiologically present during the stages of development of this tissue. These organoids recapitulate fundamental functions of ChP such as CSF secretion and formation of a tight epithelial barrier selectively permeable to small molecules. Combining single-cell RNA-sequencing with immunohistochemical and EM validation, we detected the presence of ChP specific channels and transporters localised on the apical brush border of the ChP epithelium. We are now examining the temporal development and maturation of these organoids. We found that, like ChP tissue in vivo, organoids stop proliferating in vitro and develop features of a mature tissue. Recently, we used this model to study kinetics of CSF secretion in vitro and explore disease-biomarkers that could be relevant for conditions such as normal pressure hydrocephalus. In conclusion, ChP organoids have been proven useful in multiple applications and represent a powerful tool to study not only developmental diseases but also conditions affecting adult human ChP.