Transient Deregulation of Canonical Wnt Signaling in Developing Pyramidal Neurons Leads to Dendritic Defects and Impaired Behavior.
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.
['Viale|Beatrice|B|', 'Song|Lin|L|', 'Petrenko|Volodymyr|V|', 'Wenger Combremont|Anne-Laure|AL|', 'Contestabile|Alessandro|A|', 'Bocchi|Riccardo|R|', 'Salmon|Patrick|P|', 'Carleton|Alan|A|', 'An|Lijia|L|', 'Vutskits|Laszlo|L|', 'Kiss|Jozsef Zoltan|JZ|']
D000818:Animals D002478:Cells, Cultured D003712:Dendrites D005260:Female D057809:HEK293 Cells D006801:Humans D008297:Male D055495:Neurogenesis D020933:Neurotrophin 3 D017966:Pyramidal Cells D051381:Rats D017208:Rats, Wistar D065852:Spatial Memory D060449:Wnt Signaling Pathway
Wnt dendrite retrosplenial spine dendritogenesis TCF4 spatial navigation β-catenin