Wnt/β-catenin signaling in brain development and mental disorders: keeping TCF7L2 in mind.

Canonical Wnt signaling is transduced by β-catenin and the lymphoid enhancer factor 1 (LEF1)/T cell-specific transcription factor (TCF) transcription factors and regulates many aspects of metazoan development and tissue renewal. Although much evidence has associated the canonical Wnt/β-catenin signaling with mood disorders, the mechanistic links are still unknown. Many components of the canonical Wnt pathway are involved in cellular processes that are unrelated to canonical Wnt signaling, thus further blurring the picture. The present review critically evaluates the involvement of Wnt/β-catenin signaling in developmental processes that putatively underlie the pathology of mental illnesses. Particular attention is given to the roles of LEF1/TCF transcription factors, which have been discussed surprisingly rarely in this context. Highlighting recent discoveries, we propose that alterations in the activity of LEF1/TCF, and particularly of TCF7L2, result in defects previously associated with neuropsychiatric disorders, including imbalances in neurogenesis and oligodendrogenesis, the functional disruption of thalamocortical circuitry and dysfunction of the habenula. This article is protected by copyright. All rights reserved.