Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity

Abstract 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 api...

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Autores principales:	Jerome Ezan, Maité M. Moreau, Tamrat M. Mamo, Miki Shimbo, Maureen Decroo, Melanie Richter, Ronan Peyroutou, Rivka Rachel, Fadel Tissir, Froylan Calderon de Anda, Nathalie Sans, Mireille Montcouquiol
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15321b3900c84a03a1b92220e52aea4c
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spelling	oai:doaj.org-article:15321b3900c84a03a1b92220e52aea4c2021-12-02T16:55:53ZEarly loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity10.1038/s41598-021-88147-12045-2322https://doaj.org/article/15321b3900c84a03a1b92220e52aea4c2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88147-1https://doaj.org/toc/2045-2322Abstract 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.Jerome EzanMaité M. MoreauTamrat M. MamoMiki ShimboMaureen DecrooMelanie RichterRonan PeyroutouRivka RachelFadel TissirFroylan Calderon de AndaNathalie SansMireille MontcouquiolNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jerome Ezan Maité M. Moreau Tamrat M. Mamo Miki Shimbo Maureen Decroo Melanie Richter Ronan Peyroutou Rivka Rachel Fadel Tissir Froylan Calderon de Anda Nathalie Sans Mireille Montcouquiol Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
description	Abstract 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.
format	article
author	Jerome Ezan Maité M. Moreau Tamrat M. Mamo Miki Shimbo Maureen Decroo Melanie Richter Ronan Peyroutou Rivka Rachel Fadel Tissir Froylan Calderon de Anda Nathalie Sans Mireille Montcouquiol
author_facet	Jerome Ezan Maité M. Moreau Tamrat M. Mamo Miki Shimbo Maureen Decroo Melanie Richter Ronan Peyroutou Rivka Rachel Fadel Tissir Froylan Calderon de Anda Nathalie Sans Mireille Montcouquiol
author_sort	Jerome Ezan
title	Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
title_short	Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
title_full	Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
title_fullStr	Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
title_full_unstemmed	Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
title_sort	early loss of scribble affects cortical development, interhemispheric connectivity and psychomotor activity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/15321b3900c84a03a1b92220e52aea4c
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Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity

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