LIN7A depletion disrupts cerebral cortex development, contributing to intellectual disability in 12q21-deletion syndrome.
LIN7A depletion disrupts cerebral cortex development, contributing to intellectual disability in 12q21-deletion syndrome.
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DOI：
10.1371/journal.pone.0092695
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yamagata T
中科院分区：
文献类型：
--
作者：
Matsumoto A;Mizuno M;Hamada N;Nozaki Y;Jimbo EF;Momoi MY;Nagata K;Yamagata T
在4例病例中报告了12 q21的间质性缺失，这些病例具有几个共同的临床特征，包括智力残疾（ID），低耳和轻微的心脏异常。使用Agilent Human Genome CGH 180 K阵列对一名患有这些症状以及胼胝体发育不全的2岁日本男孩的基因组DNA进行比较基因组杂交（CGH）分析。因此，在12q21.2-q21.33（nt. 77 203 574-91 264 613 bp），共检测到72个基因。其中，我们专注于LIN 7A，它编码一种对突触功能很重要的支架蛋白，作为ID的可能负责基因，我们分析了它在大脑皮层发育中的作用。Western blotting分析表明，Lin-7A在胚胎13.5天（E）表达，并在胚胎期逐渐增加。生化分馏导致富集林-7A的突触前馏分。通过RNAi抑制Lin-7A表达，在E14.5使用子宫内电穿孔，在出生后第2天（P）延迟神经元迁移，并且Lin-7A缺陷的神经元保留在皮质板的下区和中间区。此外，当Lin-7A在一个半球的皮质神经元中沉默时，对侧半球的轴突生长被延迟;这些神经元的发育被破坏，使得一半在离开胼胝体后没有延伸到对侧半球。总之，LIN 7A是一个候选基因负责12 q21缺失综合征，异常的神经元迁移和纵裂轴突发育可能有助于ID和胼胝体发育不全，分别。
Interstitial deletion of 12q21 has been reported in four cases, which share several common clinical features, including intellectual disability (ID), low-set ears, and minor cardiac abnormalities. Comparative genomic hybridization (CGH) analysis using the Agilent Human Genome CGH 180K array was performed with the genomic DNA from a two-year-old Japanese boy with these symptoms, as well as hypoplasia of the corpus callosum. Consequently, a 14 Mb deletion at 12q21.2-q21.33 (nt. 77 203 574–91 264 613 bp), which includes 72 genes, was detected. Of these, we focused on LIN7A, which encodes a scaffold protein that is important for synaptic function, as a possible responsible gene for ID, and we analyzed its role in cerebral cortex development. Western blotting analyses revealed that Lin-7A is expressed on embryonic day (E) 13.5, and gradually increases in the mouse brain during the embryonic stage. Biochemical fractionation resulted in the enrichment of Lin-7A in the presynaptic fraction. Suppression of Lin-7A expression by RNAi, using in utero electroporation on E14.5, delayed neuronal migration on postnatal day (P) 2, and Lin-7A-deficient neurons remained in the lower zone of the cortical plate and the intermediate zone. In addition, when Lin-7A was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed; development of these neurons was disrupted such that one half did not extend into the contralateral hemisphere after leaving the corpus callosum. Taken together, LIN7A is a candidate gene responsible for 12q21-deletion syndrome, and abnormal neuronal migration and interhemispheric axon development may contribute to ID and corpus callosum hypoplasia, respectively.
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影响因子：
3.3
作者：
Shinoda T;Ito H;Sudo K;Iwamoto I;Morishita R;Nagata K
通讯作者：
Nagata K
DOI：
10.1177/1073858410386384
发表时间：
2011-10
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Zheng CY;Seabold GK;Horak M;Petralia RS
通讯作者：
Petralia RS
影响因子：
3.7
作者：
Mizutani, Yoko;Ito, Hidenori;Nagata, Koh-ichi
通讯作者：
Nagata, Koh-ichi
影响因子：
25
作者：
Bai, JL;Ramos, RL;LoTurco, JJ
通讯作者：
LoTurco, JJ
影响因子：
2
作者：
Shinawi, Marwan;Sahoo, Trilochan;Beaudet, Arthur L.
通讯作者：
Beaudet, Arthur L.