Postnatal analysis of the effect of embryonic knockdown and overexpression of candidate dyslexia susceptibility gene homolog Dcdc2 in the rat
Postnatal analysis of the effect of embryonic knockdown and overexpression of candidate dyslexia susceptibility gene homolog Dcdc2 in the rat
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DOI：
10.1016/j.neuroscience.2008.01.020
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发表时间：
2008-03-27
期刊：
影响因子：
3.3
通讯作者：
Rosen, G. D.
中科院分区：
文献类型：
--
作者：
Burbridge, T. J.;Wang, Y.;Rosen, G. D.
胚胎敲低大鼠大脑皮质前体细胞候选阅读障碍易感基因（CDSG）同源物导致新皮质迁移的急性障碍。在本报告中，我们研究了胚胎敲低和过表达的同源物DCDC 2，CDSG之一，对出生后的大脑皮层组织的影响。使用窝内设计，我们用1）靶向Dcdc 2的小发夹RNA（shRNA）载体，2）DCDC 2过表达构建体，3）Dcdc 2 shRNA沿着DCDC 2过表达构建体，4）由DCDC 2的C末端结构域组成的过表达构建体，或5）由DCDC 2的DCX末端结构域组成的过表达构建体。Dcdc2的RNAi导致室周区域中的异位神经元的口袋。大约25%的转染大脑有海马锥体细胞迁移异常。Dcdc2 shRNA转染的神经元以双峰模式迁移，其中约7%的神经元从心室区迁移短距离，另外30%的神经元迁移通过其预期的层。用Dcdc2 shRNA沿着DCDC 2过表达构建体转染的大鼠挽救了室周异位表型，但不影响迁移超过其预期层位置的转染神经元的百分比。没有与任何过表达构建体相关的畸形，也没有显著的层迁移破坏。这些结果支持了Dcdc2表达的敲低导致神经元迁移障碍的说法，这些神经元迁移障碍类似于在阅读障碍者的大脑中看到的那些。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Embryonic knockdown of candidate dyslexia susceptibility gene (CDSG) homologs in cerebral cortical progenitor cells in the rat results in acute disturbances of neocortical migration. In the current report we investigated the effects of embryonic knockdown and overexpression of the homolog of DCDC2, one of the CDSGs, on the postnatal organization of the cerebral cortex. Using a within-litter design, we transfected cells in rat embryo neocortical ventricular zone around embryonic day (E) 15 with either 1) small hairpin RNA (shRNA) vectors targeting Dcdc2, 2) a DCDC2 overexpression construct, 3) Dcdc2 shRNA along with DCDC2 overexpression construct, 4) an overexpression construct composed of the C terminal domain of DCDC2, or 5) an overexpression construct composed of the DCX terminal domain of DCDC2. RNAi of Dcdc2 resulted in pockets of heterotopic neurons in the periventricular region. Approximately 25% of the transfected brains had hippocampal pyramidal cell migration anomalies. Dcdc2 shRNA-transfected neurons migrated in a bimodal pattern, with approximately 7% of the neurons migrating a short distance from the ventricular zone, and another 30% migrating past their expected lamina. Rats transfected with Dcdc2 shRNA along with the DCDC2 overexpression construct rescued the periventricular heterotopia phenotype, but did not affect the percentage of transfected neurons that migrate past their expected laminar location. There were no malformations associated with any of the overexpression constructs, nor was there a significant laminar disruption of migration. These results support the claim that knockdown of Dcdc2 expression results in neuronal migration disorders similar to those seen in the brains of dyslexics. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.