ΑT-catenin in restricted brain cell types and its potential connection to autism. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Folmsbee, Stephen; Wilcox, Douglas; Tyberghein, Koen; De Bleser, Pieter; Tourtellotte, Warren; van Hengel, Jolanda; van Roy, Frans; Gottardi, Cara
• Is Part Of: Journal of molecular psychiatry. Volume 4:Issue 1(2016)
• Page Start: 1
• Page End: 13
• Publication Date: 2016-12
• Subjects: Alpha-T-catenin -- Adherens junction -- Autism -- Alzheimer's disease -- Cerebellum -- Choroid plexus -- Ependyma -- Schizophrenia; Neuropsychiatry -- Periodicals; Mental illness -- Periodicals; Mental illness -- Molecular aspects -- Periodicals; Mental Disorders -- Periodicals; Neuropsychiatry -- Periodicals; Mental illness; Neuropsychiatry; Electronic journals; 616.8
• DOI: 10.1186/s40303-016-0017-9
• Languages: English
• ISSNs: 2049-9256

Abstract

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.