Cadherin 8 regulates proliferation of cortical interneuron progenitors.

Cadherin 8 regulates proliferation of cortical interneuron progenitors.
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DOI:
10.1007/s00429-018-1772-4
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发表时间:
2019-01
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:
Memi F;Killen AC;Barber M;Parnavelas JG;Andrews WD

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皮层中间神经元出生在前脑腹侧,在中间区(IZ)和板前区/边缘区水平切线迁移到发育中的皮层,在那里它们切换到径向迁移,然后在皮层板中定居最终位置。在之前的一次尝试中,我们鉴定了调节流规范的分子,对皮质发生过程中取自两条迁移流的gfp标记的中间神经元进行了转录组学分析。许多钙粘蛋白被发现表达差异,其中钙粘蛋白8 (Cdh8)选择性地存在于IZ流中。我们在组织切片的mRNA和蛋白水平上验证了这种表达模式,发现大约一半的IZ中间神经元表达Cdh8。此外,在皮层下的生发区也检测到这种钙粘蛋白,这表明它可能不仅参与中间神经元的迁移,还参与中间神经元的生成。在E18.5缺乏钙粘蛋白的动物皮质中间神经元的定量分析显示,它们的数量显著增加。随后的体外功能实验表明,阻断Cdh8功能导致细胞增殖增加,而过表达则相反,支持其在中间神经元生成中的作用。
Cortical interneurons are born in the ventral forebrain and migrate tangentially in two streams at the levels of the intermediate zone (IZ) and the pre-plate/marginal zone to the developing cortex where they switch to radial migration before settling in their final positions in the cortical plate. In a previous attempt to identify the molecules that regulate stream specification, we performed transcriptomic analysis of GFP-labelled interneurons taken from the two migratory streams during corticogenesis. A number of cadherins were found to be expressed differentially, with Cadherin-8 (Cdh8) selectively present in the IZ stream. We verified this expression pattern at the mRNA and protein levels on tissue sections and found approximately half of the interneurons of the IZ expressed Cdh8. Furthermore, this cadherin was also detected in the germinal zones of the subpallium, suggesting that it might be involved not only in the migration of interneurons but also in their generation. Quantitative analysis of cortical interneurons in animals lacking the cadherin at E18.5 revealed a significant increase in their numbers. Subsequent functional in vitro experiments showed that blocking Cdh8 function led to increased cell proliferation, with the opposite results observed with over-expression, supporting its role in interneuron generation.
DOI: 10.1006/geno.1997.5152
发表时间: 1998-03-01
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