Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
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Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity. / Ezan, Jerome; Moreau, Maité M; Mamo, Tamrat M; Shimbo, Miki; Decroo, Maureen; Richter, Melanie; Peyroutou, Ronan; Rachel, Rivka; Tissir, Fadel; de Anda, Froylan Calderon; Sans, Nathalie; Montcouquiol, Mireille.
in: SCI REP-UK, Jahrgang 11, Nr. 1, 27.04.2021, S. 9106.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity
AU - Ezan, Jerome
AU - Moreau, Maité M
AU - Mamo, Tamrat M
AU - Shimbo, Miki
AU - Decroo, Maureen
AU - Richter, Melanie
AU - Peyroutou, Ronan
AU - Rachel, Rivka
AU - Tissir, Fadel
AU - de Anda, Froylan Calderon
AU - Sans, Nathalie
AU - Montcouquiol, Mireille
PY - 2021/4/27
Y1 - 2021/4/27
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-021-88147-1
DO - 10.1038/s41598-021-88147-1
M3 - SCORING: Journal article
C2 - 33907211
VL - 11
SP - 9106
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
ER -