Transient Deregulation of Canonical Wnt Signaling in Developing Pyramidal Neurons Leads to Dendritic Defects and Impaired Behavior

• Published in: Cell reports (Cambridge) Vol. 27; no. 5; pp. 1487 - 1502.e6
• Main Authors: Viale, Beatrice, Song, Lin, Petrenko, Volodymyr, Wenger Combremont, Anne-Laure, Contestabile, Alessandro, Bocchi, Riccardo, Salmon, Patrick, Carleton, Alan, An, Lijia, Vutskits, Laszlo, Kiss, Jozsef Zoltan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.04.2019; Elsevier
• Subjects: dendrite; dendritogenesis; retrosplenial; spatial navigation; spine; TCF4; Wnt; β-catenin; β-catenin; dendritogenesis; retrosplenial; spatial navigation; dendrite; spine; TCF4; Wnt
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.04.026

During development, the precise implementation of molecular programs is a key determinant of proper dendritic development. Here, we demonstrate that canonical Wnt signaling is active in dendritic bundle-forming layer II pyramidal neurons of the rat retrosplenial cortex during dendritic branching and spine formation. Transient downregulation of canonical Wnt transcriptional activity during the early postnatal period irreversibly reduces dendritic arbor architecture, leading to long-lasting deficits in spatial exploration and/or navigation and spatial memory in the adult. During the late phase of dendritogenesis, canonical Wnt-dependent transcription regulates spine formation and maturation. We identify neurotrophin-3 as canonical Wnt target gene in regulating dendritogenesis. Our findings demonstrate how temporary imbalance in canonical Wnt signaling during specific time windows can result in irreversible dendritic defects, leading to abnormal behavior in the adult. [Display omitted] •Cortical neurons express high canonical Wnt signaling throughout dendritogenesis•Temporary Wnt downregulation reduces dendritic complexity and spine number•Canonical Wnt signaling regulates dendritogenesis through neurotrophin-3 expression•Dendritic defects are irreversible and lead to abnormal behavior in adult rats Viale et al. demonstrate that transient downregulation of canonical Wnt signaling transcriptional activity during early postnatal period leads to irreversible decrease in dendritic complexity and spine number. These long-term defects result in abnormal behavior in the adult rats. In the late phase, reduction in Wnt signaling affects only spine number.