title: αT-catenin in restricted brain cell types and its potential connection to autism.
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 αE-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.
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA ; The Driskill Graduate Training Program in Life Sciences, Northwestern University Feinberg School of Medicine, 240 East Huron St., McGaw Pavilion, M-323, Chicago, IL 60611 USA.
authors.forename: Stephen Sai
authors.initials: SS
authors.lastname: Folmsbee
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA ; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA ; The Driskill Graduate Training Program in Life Sciences, Northwestern University Feinberg School of Medicine, 240 East Huron St., McGaw Pavilion, M-323, Chicago, IL 60611 USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Wilcox
authors.affiliation: Department of Biomedical Molecular Biology, Molecular Cell Biology Unit, Ghent University, Ghent, Belgium ; Inflammation Research Center, Flanders Institute for Biotechnology (VIB), B-9052 Ghent, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Tyberghein
authors.affiliation: Department of Biomedical Molecular Biology, Molecular Cell Biology Unit, Ghent University, Ghent, Belgium ; Inflammation Research Center, Flanders Institute for Biotechnology (VIB), B-9052 Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: De Bleser
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA ; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA ; The Driskill Graduate Training Program in Life Sciences, Northwestern University Feinberg School of Medicine, 240 East Huron St., McGaw Pavilion, M-323, Chicago, IL 60611 USA.
authors.forename: Warren G
authors.initials: WG
authors.lastname: Tourtellotte
authors.affiliation: Department of Biomedical Molecular Biology, Molecular Cell Biology Unit, Ghent University, Ghent, Belgium ; Inflammation Research Center, Flanders Institute for Biotechnology (VIB), B-9052 Ghent, Belgium ; Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
authors.forename: Jolanda
authors.initials: J
authors.lastname: van Hengel
authors.affiliation: Department of Biomedical Molecular Biology, Molecular Cell Biology Unit, Ghent University, Ghent, Belgium ; Inflammation Research Center, Flanders Institute for Biotechnology (VIB), B-9052 Ghent, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: van Roy
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA ; Department of Cellular and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA ; The Driskill Graduate Training Program in Life Sciences, Northwestern University Feinberg School of Medicine, 240 East Huron St., McGaw Pavilion, M-323, Chicago, IL 60611 USA.
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Gottardi
keywords: Adherens junction; Alpha-T-catenin; Alzheimer’s disease; Autism; Cerebellum; Choroid plexus; Ependyma; Schizophrenia