Active Cells, Biochemistry & Physiology Genetics & Molecular Biology

Modelling human choroid plexus development and the regulation of cerebrospinal fluid in health and disease

Funder Wellcome Charity-funded
Recipient organisation Ukri-Mrc
Funding £3.2M
Period Oct 2023 — Oct 2031

In plain English

AI plain-English summary

A single layer of cells in the brain, the choroid plexus, pumps out the cerebrospinal fluid that bathes the developing brain, and researchers now want to watch that process go wrong in a lab dish. This matters because the fluid is not just a cushion—it carries signals, hormones, and nutrients that guide how neural stem cells build the brain. When the fluid’s composition or flow is disrupted, it can lead to microcephaly, autism, or schizophrenia. Yet the early development of the choroid plexus itself remains poorly understood, partly because it is difficult to study in human embryos. The researcher has created miniature choroid plexus organoids—tiny, lab-grown versions of the tissue—and will use them to map which cell types produce which fluid components, and how those signals shape the developing cortex. They will also investigate how immune cells cross the blood-CSF barrier, both in healthy brains and in multiple sclerosis. This is fundamental science. It will not yield a drug or diagnostic tomorrow. But understanding how the choroid plexus builds and regulates the brain’s chemical bath is a necessary step toward explaining—and eventually preventing—neurodevelopmental disorders that begin before birth.

View original technical description
Our brain is floating in the cerebrospinal fluid (CSF): a source of signaling factors, hormones and nutrients. The CSF is secreted by a single layer of cells called the choroid plexus (ChP), which forms the blood-CSF-barrier. The dynamic regulation of CSF signals delivered to the neural stem cells is critical for brain development. CSF abnormalities can lead to diseases such as microcephaly, autism and schizophrenia. My plan is to use the new model I recently developed of ChP organoids to better understand the dynamic changes in early ChP and CSF and how they influence brain development. First, using single-cell RNA sequencing and proteomics, we will study the origin of cellular diversity in the ChP and the contribution of different cell subtypes to the CSF proteome. We will validate these findings with foetal ChP tissue. Next, using ChP-cortical organoid, we will explore how CSF signals influence cortical development. We will investigate the effect of temporal secretion of CSF components on the neuroepithelial cell proliferation and differentiation using synchronised trafficking assays. Finally, we will investigate the role of the barrier in transport of immune cells across the ChP epithelium, characterise the trafficking mechanisms in health and diseases such as multiple sclerosis (MS).

View the original record at the funder ↗

Researchers

Laura Pellegrini (EPMC Awardee)

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Original classification

Career Development Award

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