Position of neocortical neurons transfected at different gestational ages with shRNA targeted against candidate dyslexia susceptibility genes.
Position of neocortical neurons transfected at different gestational ages with shRNA targeted against candidate dyslexia susceptibility genes.
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DOI：
10.1371/journal.pone.0065179
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rosen GD
中科院分区：
文献类型：
--
作者：
Adler WT;Platt MP;Mehlhorn AJ;Haight JL;Currier TA;Etchegaray MA;Galaburda AM;Rosen GD
发展性阅读障碍是一种语言学习障碍，影响约4-10%的人口。目前已鉴定出许多阅读障碍易感基因，包括位于染色体6p22.2的DCDC 2和KIAA 0319以及位于染色体15 q21的DYX 1C 1。胚胎敲低这些基因的同源物在大鼠新皮质投射细胞祖细胞的功能，在子宫内电穿孔的质粒编码的小发夹RNA（shRNA）显示，所有三个基因破坏神经元迁移到新皮质。具体而言，这种破坏将导致异位形成（Dyx 1c 1和Kiaa 0319）和/或过度迁移超过其预期的椎板位置（Dyx 1c 1和Dcdc 2）。在这些实验中，在胚胎第15.5天（E）转染了通常去往上新皮质层的神经元，我们设计了实验来测试这些迁移表型是否是靶向特定类型投射神经元的结果。我们在三个胎龄（E14.5、E15.5或E16.5）分别用Dcdc 2 shRNA、Dyx 1c 1 shRNA、Kiaa 0319 shRNA或荧光蛋白（作为对照）转染窝仔。让幼崽足月，在3周龄时检查它们的大脑，以确定转染细胞的位置。我们发现转染的年龄并不影响未迁移神经元的百分比，Kiaa 0319 shRNA转染导致在所有三个年龄的异位形成。过度迁移的神经元转染Dcdc 2 shRNA，而目前在以后的年龄转染后，并没有发生E14.5转染。这些结果被认为是在光的已知功能，这些候选人的阅读障碍易感基因。
Developmental dyslexia is a language learning disorder that affects approximately 4–10% of the population. A number of candidate dyslexia susceptibility genes have been identified, including DCDC2 and KIAA0319 on Chromosome (Chr) 6p22.2 and DYX1C1 on Chr 15q21. Embryonic knockdown of the function of homologs of these genes in rat neocortical projection cell progenitors by in utero electroporation of plasmids encoding small hairpin RNA (shRNA) revealed that all three genes disrupted neuronal migration to the neocortex. Specifically, this disruption would result in heterotopia formation (Dyx1c1 and Kiaa0319) and/or overmigration past their expected laminar location (Dyx1c1 and Dcdc2). In these experiments, neurons normally destined for the upper neocortical laminæ were transfected on embryonic day (E) 15.5, and we designed experiments to test whether these migration phenotypes were the result of targeting a specific type of projection neuron. We transfected litters with Dcdc2 shRNA, Dyx1c1 shRNA, Kiaa0319 shRNA, or fluorescent protein (as a control) at each of three gestational ages (E14.5, E15.5, or E16.5). Pups were allowed to come to term, and their brains were examined at 3 weeks of age for the position of transfected cells. We found that age of transfection did not affect the percentage of unmigrated neurons—transfection with Kiaa0319 shRNA resulted in heterotopia formation at all three ages. Overmigration of neurons transfected with Dcdc2 shRNA, while present following transfections at the later ages, did not occur following E14.5 transfections. These results are considered in light of the known functions of each of these candidate dyslexia susceptibility genes.
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影响因子：
11.2
作者：
HUMPHREYS, P;KAUFMANN, WE;GALABURDA, AM
通讯作者：
GALABURDA, AM
DOI：
10.1002/ajmg.b.30018
发表时间：
2004-11-15
影响因子：
2.8
作者：
Chapman, NH;Igo, RP;Raskind, WH
通讯作者：
Raskind, WH
影响因子：
9.8
作者：
Cope, N;Harold, D;Williams, J
通讯作者：
Williams, J
影响因子：
2.1
作者：
Hatakeyama, S;Matsumoto, M;Nakayama, KI
通讯作者：
Nakayama, KI
影响因子：
3.3
作者：
Burbridge, T. J.;Wang, Y.;Rosen, G. D.
通讯作者：
Rosen, G. D.