Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
MOREAU, Maite M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MAMO, Tamrat M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
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Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MOREAU, Maite M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MAMO, Tamrat M.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
DECROO, Maureen
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
PEYROUTOU, Ronan
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
SANS, Nathalie
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MONTCOUQUIOL, Mireille
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
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Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Langue
EN
Article de revue
Ce document a été publié dans
Scientific Reports. 2021-04-27, vol. 11, n° 1
Résumé en anglais
Neurodevelopmental disorders arise from combined defects in processes including cell proliferation, differentiation, migration and commissure formation. The evolutionarily conserved tumor-suppressor protein Scribble (Scrib) ...Lire la suite >
Neurodevelopmental disorders arise from combined defects in processes including cell proliferation, differentiation, migration and commissure formation. The evolutionarily conserved tumor-suppressor protein Scribble (Scrib) serves as a nexus to transduce signals for the establishment of apicobasal and planar cell polarity during these processes. Human SCRIB gene mutations are associated with neural tube defects and this gene is located in the minimal critical region deleted in the rare Verheij syndrome. In this study, we generated brain-specific conditional cKO mouse mutants and assessed the impact of the Scrib deletion on brain morphogenesis and behavior. We showed that embryonic deletion of Scrib in the telencephalon leads to cortical thickness reduction (microcephaly) and partial corpus callosum and hippocampal commissure agenesis. We correlated these phenotypes with a disruption in various developmental mechanisms of corticogenesis including neurogenesis, neuronal migration and axonal connectivity. Finally, we show that Scrib cKO mice have psychomotor deficits such as locomotor activity impairment and memory alterations. Altogether, our results show that Scrib is essential for early brain development due to its role in several developmental cellular mechanisms that could underlie some of the deficits observed in complex neurodevelopmental pathologies.< Réduire
Projet Européen
Network of European funding for Neuroscience research
Project ANR
Caractérisations moléculaire et fonctionnelle de la protéine Scribble 1 au cours du développement du système nerveux central - ANR-07-NEUR-0031
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043
Unités de recherche