Transient Deregulation of Canonical Wnt Signaling in Developing Pyramidal Neurons Leads to Dendritic Defects and Impaired Behavior
Beatrice Viale,
Lin Song,
Volodymyr Petrenko,
Anne-Laure Wenger Combremont,
Alessandro Contestabile,
Riccardo Bocchi,
Patrick Salmon,
Alan Carleton,
Lijia An,
Laszlo Vutskits,
Jozsef Zoltan Kiss
Affiliations
Beatrice Viale
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland
Lin Song
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland; School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, China
Volodymyr Petrenko
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland
Anne-Laure Wenger Combremont
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland
Alessandro Contestabile
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland
Riccardo Bocchi
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland
Patrick Salmon
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland
Alan Carleton
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland
Lijia An
School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, China
Laszlo Vutskits
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland; Department of Anesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, 1211 Geneva 4, Switzerland
Jozsef Zoltan Kiss
Department of Basic Neurosciences, University of Geneva Medical School, 1211 Geneva 4, Switzerland; Corresponding author
Summary: 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 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. Keywords: dendrite, dendritogenesis, spine, Wnt, β-catenin, TCF4, retrosplenial, spatial navigation
