Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior
| العنوان: | Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior |
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| المؤلفون: | Riccardo Bocchi, Patrick Salmon, Charles Quairiaux, Michael Boitard, Kristof Egervari, Mathias De Roo, Jozsef Zoltan Kiss, Suzanne Oskouie, Laura Carol-Perdiguer, Beatrice Viale |
| المصدر: | Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017) Nature Communications Nature Communications, Vol. 8, No 1 (2017) P. 1158 |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Neurogenesis, Science, Regulator, General Physics and Astronomy, Biology, Somatosensory system, Article, General Biochemistry, Genetics and Molecular Biology, Corpus Callosum, Membrane Potentials, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Cell Movement, Image Processing, Computer-Assisted, Animals, Humans, Premovement neuronal activity, Rats, Wistar, lcsh:Science, Social Behavior, Cerebrum, Wnt Signaling Pathway, Neurons, Multidisciplinary, Behavior, Animal, Sequence Analysis, RNA, HEK 293 cells, Wnt signaling pathway, Brain, Somatosensory Cortex, General Chemistry, ddc:616.8, Rats, Cortex (botany), Wnt Proteins, HEK293 Cells, Phenotype, 030104 developmental biology, lcsh:Q, Female, Neuroglia, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | 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. Functional consequence of transient delay in neuronal migration is unclear. This study shows that Wnt/C-Kit signaling regulates radial migration in rat somatosensory cortex, and that transient delay of L2/3 neuronal migration leads to interhemispheric connectivity alteration and abnormal social behavior. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::45fcd01e9c84958905f7d02ab0a581b8 https://doaj.org/article/8d2f9638ad8e4f4bba3636fccca2602d |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....45fcd01e9c84958905f7d02ab0a581b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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