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Molecular heterogeneity in the choroid plexus epithelium: the 22‐member γ‐protocadherin family is differentially expressed, apically localized, and implicated in CSF regulation
Author(s) -
Lobas Mark A.,
Helsper Lindsey,
Ver Claire G.,
Schreiner Dietmar,
Zhang Yong,
Holtzman Michael J.,
Thedens Daniel R.,
Weiner Joshua A.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07587.x
Subject(s) - choroid plexus , adherens junction , biology , immunostaining , protocadherin , microbiology and biotechnology , ependyma , epithelium , tight junction , epithelial polarity , cadherin , pathology , anatomy , neuroscience , immunology , central nervous system , cell , genetics , immunohistochemistry , medicine
J. Neurochem. (2012) 120 , 913–927. Abstract The choroid plexus (CP) epithelium develops from the ependyma that lines the ventricular system, and plays a critical role in the development and function of the brain. In addition to being the primary site of CSF production, the CP maintains the blood–CSF barrier via apical tight junctions between epithelial cells. Here we show that the 22‐member γ‐protocadherin (γ‐Pcdh) family of cell adhesion molecules, which we have implicated previously in synaptogenesis and neuronal survival, is highly expressed by both CP epithelial and ependymal cells, in which γ‐Pcdh protein localization is, surprisingly, tightly restricted to the apical membrane. Multi‐label immunostaining demonstrates that γ‐Pcdhs are excluded from tight junctions, basolateral adherens junctions, and apical cilia tufts. RT‐PCR analysis indicates that, as a whole, the CP expresses most members of the Pcdh‐γ gene family. Immunostaining using novel monoclonal antibodies specific for single γ‐Pcdh proteins shows that individual epithelial cells differ in their apically localized γ‐Pcdh repertoire. Restricted mutation of the Pcdh‐γ locus in the choroid plexus and ependyma leads to significant reductions in ventricular volume, without obvious disruptions of epithelial apical‐basal polarity. Together, these results suggest an unsuspected role for the γ‐Pcdhs in CSF production and demonstrate a surprising molecular heterogeneity in the CP epithelium.