Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior.
Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior.
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DOI：
10.1038/s41467-017-01046-w
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发表时间：
2017-10-27
影响因子：
16.6
通讯作者：
Kiss JZ
中科院分区：
文献类型：
--
作者：
Bocchi R;Egervari K;Carol-Perdiguer L;Viale B;Quairiaux C;De Roo M;Boitard M;Oskouie S;Salmon P;Kiss JZ
神经细胞迁移和回路发育受扰与神经发育疾病的发病机制有关；然而，将这些发育错误与行为改变联系起来的直接步骤仍不清楚。在这里，我们证明了Wnt/C-Kit信号是大鼠躯体感觉皮质神经胶质细胞引导的径向迁移的关键调节因子。暂时性下调移行中的Wnt信号，导致在第2/3层的定位延迟。延迟的神经元表现为神经元活动减少，传入连接受损，导致永久的膝状体投射缺陷。有这些缺陷的动物表现出躯体感觉功能改变，社交互动减少，重复动作减少。在出生后的关键时期，通过过度表达Wnt下游效应器C-Kit或选择性地激活穹隆投射神经元来恢复正常的迁移，可以防止大脑半球间的异常连接和行为改变。我们的发现确定了典型的Wnt信号缺陷、神经元迁移延迟、大脑半球间连接缺陷和类似人类自闭症特征的异常社会行为之间的联系。神经元迁移的暂时性延迟的功能后果尚不清楚。本研究表明，Wnt/C-Kit信号调节大鼠躯体感觉皮层的径向迁移，L2/3神经元迁移的一过性延迟导致大脑半球间连通性改变和异常的社会行为。
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.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
16.2
作者：
He S;Li Z;Ge S;Yu YC;Shi SH
通讯作者：
Shi SH
DOI：
10.1146/annurev-cellbio-101512-122400
发表时间：
2013
影响因子：
11.3
作者：
Evsyukova I;Plestant C;Anton ES
通讯作者：
Anton ES
影响因子：
5.2
作者：
Cajanek, Lukas;Ribeiro, Diogo;Arenas, Ernest
通讯作者：
Arenas, Ernest
影响因子：
3.7
作者：
Hirsch, Cordula;Campano, Louise M.;Hecht, Andreas
通讯作者：
Hecht, Andreas