Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior

Article Article scientifique Article Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior eng 2017 author Bocchi Riccardo 634138 author Egervari Kristof Levente 0000-0001-6763-9069 761273 author Carol Perdiguer Laura 822920 author Viale Beatrice 781695 author Quairiaux Charles 0000-0003-3770-8232 640914 author De Roo Mathias 629721 author Boitard Michael 668765 author Oskouie Suzanne 810527 author Salmon Patrick 505385 author Kiss Jozsef Zoltan 22758 1158 10.1038/s41467-017-01046-w 29079819 2041-1723 Perturbed neuronal migration and circuit development have been implicated in the pathogenesis of neurodevelopmental diseases; however, the direct steps linking these developmental errors to behavior alterations remain unknown. Here we demonstrate that Wnt/C-Kit signaling is a key regulator of glia-guided radial migration in rat somatosensory cortex. Transient downregulation of Wnt signaling in migrating, callosal projection neurons results in delayed positioning in layer 2/3. Delayed neurons display reduced neuronal activity with impaired afferent connectivity causing permanent deficit in callosal projections. Animals with these defects exhibit altered somatosensory function with reduced social interactions and repetitive movements. Restoring normal migration by overexpressing the Wnt-downstream effector C-Kit or selective chemogenetic activation of callosal projection neurons during a critical postnatal period prevents abnormal interhemispheric connections as well as behavioral alterations. Our findings identify a link between defective canonical Wnt signaling, delayed neuronal migration, deficient interhemispheric connectivity and abnormal social behavior analogous to autistic characteristics in humans. Dewey 616.8 53 Département de neurosciences fondamentales 21A false 112 Progéniteurs neuronaux 141 Nature Communications 8 1 85390904-2e9b-42df-97af-34e9d58ab26c Article (Published version) Public s41467-017-01046-w.pdf 4634448 application/pdf CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior	Nature Communications			2017	531	304

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Carol Perdiguer, Laura