Overexpression of the 14-3-3gamma protein in embryonic mice results in neuronal migration delay in the developing cerebral cortex
Overexpression of the 14-3-3gamma protein in embryonic mice results in neuronal migration delay in the developing cerebral cortex
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DOI：
10.1016/j.neulet.2016.06.009
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发表时间：
2016-08-15
影响因子：
2.5
通讯作者：
Toyo-oka, Kazuhito
中科院分区：
文献类型：
--
作者：
Cornell, Brett;Wachi, Tomoka;Toyo-oka, Kazuhito
14-3-3蛋白家族是一组在大脑中高度表达的多功能蛋白；然而，它们在大脑发育中的功能在很大程度上是未知的。威廉姆斯综合征是一种由7q11.23染色体位点缺失引起的神经发育障碍，包括编码14-3-3 γ的基因，导致发育迟缓、智力残疾和癫痫。我们之前已经证明，在小鼠子宫内敲除14-3-3 - γ蛋白会导致皮层锥体神经元的神经元迁移延迟。重要的是，在威廉姆斯综合征中，7q11.23位点被复制，导致癫痫和智力残疾。因此，7q11.23染色体位点的缺失或重复导致癫痫。结合神经元迁移缺陷是癫痫发病的主要原因之一这一事实，我们分析了14-3-3 γ过表达是否会导致神经元迁移缺陷。在这项工作中，我们发现子宫内发育中的小鼠皮层中14-3-3 - γ的过度表达会导致锥体神经元迁移的延迟，这与之前观察到的14-3-3 - γ被敲低时的情况相似。这些结果与我们之前的研究相结合，表明在皮层发育过程中需要14-3-3 - γ表达的平衡，以防止神经元迁移的延迟。这项工作为14-3-3 γ参与神经发育障碍提供了明确的证据，以及14-3-3 γ表达的中断如何导致7q11.23位点改变时出现的神经发育障碍。2016爱思唯尔爱尔兰有限公司版权所有。
The 14-3-3 protein family is a group of multifunctional proteins that are highly expressed in the brain; however, their functions in brain development are largely unknown. Williams Syndrome is a neurodevelopmental disorder caused by a deletion in the 7q11.23 chromosome locus, including the gene encoding 14-3-3gamma, resulting in developmental delay, intellectual disabilities and epilepsy. We have previously shown that knocking down the 14-3-3gamma protein in utero in mice results in delays in neuronal migration of pyramidal neurons in the cortex. Importantly, there is a reciprocal duplication syndrome to Williams Syndrome where the 7q11.23 locus is duplicated, resulting in epilepsy and intellectual disabilities. Thus, the deletion or the duplication of the 7q11.23 chromosome locus results in epilepsy. Taken together with the fact that defects in neuronal migration are one of main causes for epilepsy, we analyzed if the overexpression of 14-3-3gamma causes neuronal migration defects. In this work, we found that the overexpression of 14-3-3gamma in utero in the developing mouse cortex results in delays in pyramidal neuron migration, similar to what was previously observed when 14-3-3gamma was knocked down. These results, in conjunction with our previous research, indicate that a balance of 14-3-3gamma expression is required during cortical development to prevent delays in neuronal migration. This work provides clear evidence as to the involvement of 14-3-3gamma in neurodevelopmental disorders and how a disruption in 14-3-3gamma expression may contribute to the neurodevelopmental disorders that manifest when the 7q11.23 locus is altered. (C) 2016 Elsevier Ireland Ltd. All rights reserved.