αT-catenin in restricted brain cell types and its potential connection to autism

Stephen Sai Folmsbee, Douglas R. Wilcox, Koen Tyberghein, Pieter De Bleser, Warren G. Tourtellotte, Jolanda van Hengel, Frans van Roy, Cara J. Gottardi*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Recent genetic association studies have linked the cadherin-based adherens junction protein alpha-T-catenin (αT-cat, CTNNA3) with the development of autism. Where αT-cat is expressed in the brain, and how its loss could contribute to this disorder, are entirely unknown. Methods: We used the αT-cat knockout mouse to examine the localization of αT-cat in the brain, and we used histology and immunofluorescence analysis to examine the neurobiological consequences of its loss. Results: We found that αT-cat comprises the ependymal cell junctions of the ventricles of the brain, and its loss led to compensatory upregulation of aE-cat expression. Notably, αT-cat was not detected within the choroid plexus, which relies on cell junction components common to typical epithelial cells. While αT-cat was not detected in neurons of the cerebral cortex, it was abundantly detected within neuronal structures of the molecular layer of the cerebellum. Although αT-cat loss led to no overt differences in cerebral or cerebellar structure, RNA-sequencing analysis from wild type versus knockout cerebella identified a number of disease-relevant signaling pathways associated with αT-cat loss, such as GABA-A receptor activation. Conclusions: These findings raise the possibility that the genetic associations between αT-cat and autism may be due to ependymal and cerebellar defects, and highlight the potential importance of a seemingly redundant adherens junction component to a neurological disorder.

Original languageEnglish (US)
Article number2
JournalJournal of Molecular Psychiatry
Volume4
Issue number1
DOIs
StatePublished - 2016

Keywords

  • Adherens junction
  • Alpha-T-catenin
  • Alzheimer's disease
  • Autism
  • Cerebellum
  • Choroid plexus
  • Ependyma
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Folmsbee, S. S., Wilcox, D. R., Tyberghein, K., De Bleser, P., Tourtellotte, W. G., Hengel, J. V., van Roy, F., & Gottardi, C. J. (2016). αT-catenin in restricted brain cell types and its potential connection to autism. Journal of Molecular Psychiatry, 4(1), [2]. https://doi.org/10.1186/s40303-016-0017-9