Journal Article

Development and functions of the choroid plexus–cerebrospinal fluid system

Lehtinen, Maria K., Lun, Melody P., Monuki, Edwin S.

2015

Overview

Key Points The choroid plexus (ChP) is a secretory tissue found in each of the brain ventricles, the main function of which is to produce cerebrospinal fluid (CSF). Although the ChP–CSF system is essential for proper development of the nervous system owing to fluid pressure within the ventricles as well as myriad CSF-borne signalling factors, it is nevertheless one of the most understudied areas of neurobiology. A highly organized tissue, the ChP consists of simple cuboidal epithelial cells surrounding a core of fenestrated capillaries and connective tissue. As the interface between peripheral circulation and the CNS, the ChP forms the blood–CSF barrier via tight junctions between adjacent epithelial cells to restrict free passage of solutes from blood into CSF, and vice versa. The ChP is present in chordates above the lancelet, and its development, which is classically categorized into four stages on the basis of its histological appearance, occurs in a stereotyped manner. Further, the order of ChP development seems to be conserved across species, with the hindbrain (fourth ventricle) ChP appearing first, followed by the bilateral appearance of the telencephalic (lateral ventricle) ChP, and the diencephalic (third ventricle) ChP appearing last. The cell-intrinsic and -extrinsic molecular mechanisms that regulate ChP development are just now being elucidated. Although ChP epithelial cells are derived from neuroepithelial progenitors, they are non-neural cells in their mature state, suggesting the need to suppress neural character in favour of a non-neural cell fate. Genetic fate-mapping studies have illustrated that cells contributing to the telencephalic ChP and hindbrain ChP exhibit lineage segregation in the mature tissues. Moreover, the ChPs are transcriptionally heterogeneous, a trait that appears to be evolutionarily conserved from mice to humans. Recent work in the field has identified several ChP-derived factors with important roles in the developing and adult brain. Importantly, the ChP epithelial cell secretome has been described, suggesting a role for a ventricle-specific, regionalized CSF in the developing brain. The health of the vertebrate brain is dependent on appropriate levels of cerebrospinal fluid (CSF), which is secreted by the choroid plexus (ChP). In this Review, Lehtinen and colleagues examine ChP structure and development and explore recently discovered functions of the ChP–CSF system. The choroid plexus (ChP) is the principal source of cerebrospinal fluid (CSF), which has accepted roles as a fluid cushion and a sink for nervous system waste in vertebrates. Various animal models have provided insights into how the ChP–CSF system develops and matures. In addition, recent studies have uncovered new, active roles for this dynamic system in the regulation of neural stem cells, critical periods and the overall health of the nervous system. Together, these findings have brought about a paradigm shift in our understanding of brain development and health, and have stimulated new initiatives for the treatment of neurological disease.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 14 / 38 / 631/378/2183 / 631/378/2571/2578 / 631/45/612/1224 / Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological Techniques / Biomedicine / Blood vessels / Brain / Cerebrospinal fluid / Cerebrospinal Fluid - physiology / Choroid plexus / Choroid Plexus - growth & development / Choroid Plexus - physiology / Humans / Medical research / Medicine / Medicine, Experimental / Nervous system / Nervous system diseases / Neurobiology / Neurosciences / Pathology / review-article / Spinal cord / Stem cells / Vertebrates