Protective role of Cadherin 13 in interneuron development.

Protective role of Cadherin 13 in interneuron development.
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DOI:
10.1007/s00429-017-1418-y
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发表时间:
2017-11
影响因子:
3.1
通讯作者:
Andrews WD
Andrews WD
中科院分区:
医学3区
文献类型:
--
作者:
Killen AC;Barber M;Paulin JJW;Ranscht B;Parnavelas JG;Andrews WD

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皮质中间神经元在神经节隆起中产生,并通过腹侧和背侧端脑迁移,然后在皮质板内找到其最终位置。在迁移的早期阶段,这些细胞存在于发育中的皮层内的两个明确的流中。为了鉴定可能在中间神经元流规范中发挥作用的候选基因,我们之前进行了微阵列分析,鉴定了在这些流中差异表达的许多钙粘蛋白受体,包括钙粘蛋白-13 (Cdh13)。表达分析证实 Cdh13 存在于 E13.5 的前板层中,并且在发育后期,存在于一些皮质中间神经元和锥体细胞中。对 E18.5 而非 E15.5 的 Cdh13 敲除小鼠进行的分析表明,中间神经元和晚生锥体神经元的数量减少,并且皮质中的凋亡细胞随之增加。这些观察结果在使用过表达和短干扰 RNA (siRNA) 构建体和显性失活抑制蛋白的分离细胞培养物中得到证实。我们的研究结果确定了 Cdh13 在皮质神经元发育中的新保护作用。
Cortical interneurons are generated in the ganglionic eminences and migrate through the ventral and dorsal telencephalon before finding their final positions within the cortical plate. During early stages of migration, these cells are present in two well-defined streams within the developing cortex. In an attempt to identify candidate genes which may play a role in interneuron stream specification, we previously carried out a microarray analysis which identified a number of cadherin receptors that were differentially expressed in these streams, including Cadherin-13 (Cdh13). Expression analysis confirmed Cdh13 to be present in the preplate layer at E13.5 and, later in development, in some cortical interneurons and pyramidal cells. Analysis of Cdh13 knockout mice at E18.5, but not at E15.5, showed a reduction in the number of interneurons and late born pyramidal neurons and a concomitant increase in apoptotic cells in the cortex. These observations were confirmed in dissociated cell cultures using overexpression and short interfering RNAs (siRNAs) constructs and dominant negative inhibitory proteins. Our findings identified a novel protective role for Cdh13 in cortical neuron development.
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