Claudin-1, -2 and -3 Are Selectively Expressed in the Epithelia of the Choroid Plexus of the Mouse from Early Development and into Adulthood While Claudin-5 is Restricted to Endothelial Cells

Abstract

A primary function of epithelial and endothelial monolayers is the formation of barriers that separate tissues into functional compartments. Tight junctions (TJs) seal the intercellular space between the single cells of a monolayer. TJs thus contribute importantly to the homeostasis of the cerebrospinal fluid as they help in maintaining the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (CSF). The composition of TJs differs by its localization as well as the stage of development according to its respective function. Claudin-3 is typically present in the epithelia and has been claimed to be a constituent of the BBB. It is, however, notoriously difficult to demonstrate its expression in endothelial cells of the brain vasculature at the morphological level by means of immunohistochemical techniques. Using an improved fixation strategy (4% paraformaldehyde at pH 11, in the presence of EDTA) and the sensitive alkaline phosphatase as a detection system, we show that claudin-3 is present in mouse epithelia from embryonic day 14 onwards. In brain, it is restricted to the anlage of choroid plexus in the ventricles, together with claudin-1 and -2. In adult mice, it is clearly delineating the epithelium of the choroid plexus in the lateral and fourth ventricles. In contrast, in cerebral blood vessels claudin-3 as well as claudin-1 and -2 are absent in cerebral blood vessels during all developmental stages up to adulthood. Rather, the BBB is characterized by the presence of claudin-5, ZO-1 and occludin. Thus, in mice claudin-3 is an important constituent of TJ in the embryonic and in the adult choroid plexus.

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…Similar data concerning claudin-1, -2, and -3 ontogenic regulation were reported for rat, mouse, and human choroid plexus [74,146]. Importantly, the barrier forming claudin-1 and -3 appear very rapidly after the choroid plexuses start to bulge in the ventricles and differentiate (Fig.…”

“…Besides these three major claudins, a number of other barrier forming and channel forming claudins are expressed in the choroid plexus [74], and some of them, such as claudin-9 and -19 have been immunodetected in apical junctions of the rat choroidal epithelium. Claudin-5, the prototypical BBB claudin, distributes at the junctions in large penetrating stromal vessels in rat and mouse and possibly in some smaller vessels [74,82,146]. Its expression in the choroidal epithelium was not detected in rat and mouse, but was recently described in human neonates [164].…”

Infectious immunity in the central nervous system and brain function

“…The meningeal arachnoid membrane and ventricular choroid plexus epithelial cells have intercellular tight junctions, comprising claudins 1, 2 and 3 (ref. 23), that help restrict the invasion of pathogens into the CNS parenchyma. CSF circulates throughout the ventricular system and subarachnoid space of the meninges via apertures between these compartments 24 , allowing detection of pathogens via meningeal CSF sampling.…”

Blood–brain barrier and its function during inflammation and autoimmunity

“…The down‐regulation of claudin‐5 expression results in the BBB disruption during CNS inflammation . Claudin‐1, ‐2, ‐3 and ‐11 molecules are known to express at choroid plexus epithelial cells and form the TJs of BCB …”

“…52 Claudin-1, -2, -3 and -11 molecules are known to express at choroid plexus epithelial cells and form the TJs of BCB. 53 Occludin was the first discovered TJ protein. It is a type-II transmembrane protein (65 kDa), with 4 transmembrane domains having In human and mice, JAM-A is also expressed on the surface of monocytes, neutrophils, T-and B-lymphocytes.…”