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

Bocchi, Riccardo; Egervari, Kristof Levente; Carol Perdiguer, Laura; Viale, Beatrice; Quairiaux, Charles; De Roo, Mathias; Boitard, Michael; Oskouie, Suzanne; Salmon, Patrick; Kiss, Jozsef Zoltan

doi:10.1038/s41467-017-01046-w

Scientific article

English

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

Contributors

Bocchi, Riccardo; Egervari, Kristof Levente

; Carol Perdiguer, Laura; Viale, Beatrice; Quairiaux, Charles

; De Roo, Mathias; Boitard, Michael; Oskouie, Suzanne; Salmon, Patrick; Kiss, Jozsef Zoltan

Published in

Nature Communications, vol. 8, no. 1, 1158

Publication date

2017

Abstract

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.

UNIGE affiliation entities

Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

UNIGE research groups

Progéniteurs neuronaux (141)

Citation (ISO format)

BOCCHI, Riccardo et al. Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior. In: Nature Communications, 2017, vol. 8, n° 1, p. 1158. doi: 10.1038/s41467-017-01046-w

Article (Published version)

CC BY

Identifiers

PID : unige:101830
DOI : 10.1038/s41467-017-01046-w
PMID : 29079819

Journal ISSN

2041-1723

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Creation

11/01/2018 10:30:00

First validation

11/01/2018 10:30:00

Update

13/10/2025 19:21:28

Status update

15/03/2023 07:49:07

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27/10/2026 15:08:46

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

Contributors

Published in

Publication date

Abstract

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

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Technical informations

Creation

First validation

Update

Status update

Last indexation