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首页> 美国卫生研究院文献>Molecular Brain >Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum
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Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum

机译：自闭症危险基因Cdh11和Cdh9在小脑自闭症相关区域的分离表达

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Results of recent genome-wide association studies (GWAS) and whole genome sequencing (WGS) highlighted type II cadherins as risk genes for autism spectrum disorders (ASD). To determine whether these cadherins may be linked to the morphogenesis of ASD-relevant brain regions, in situ hybridization (ISH) experiments were carried out to examine the mRNA expression profiles of two ASD-associated cadherins, Cdh9 and Cdh11, in the developing cerebellum. During the first postnatal week, both Cdh9 and Cdh11 were expressed at high levels in segregated sub-populations of Purkinje cells in the cerebellum, and the expression of both genes was declined as development proceeded. Developmental expression of Cdh11 was largely confined to dorsal lobules (lobules VI/VII) of the vermis as well as the lateral hemisphere area equivalent to the Crus I and Crus II areas in human brains, areas known to mediate high order cognitive functions in adults. Moreover, in lobules VI/VII of the vermis, Cdh9 and Cdh11 were expressed in a complementary pattern with the Cdh11-expressing areas flanked by Cdh9-expressing areas. Interestingly, the high level of Cdh11 expression in the central domain of lobules VI/VII was correlated with a low level of expression of the Purkinje cell marker calbindin, coinciding with a delayed maturation of Purkinje cells in the same area. These findings suggest that these two ASD-associated cadherins may exert distinct but coordinated functions to regulate the wiring of ASD-relevant circuits in the cerebellum.Electronic supplementary materialThe online version of this article (10.1186/s13041-019-0461-4) contains supplementary material, which is available to authorized users.
机译：最近的全基因组关联研究（GWAS）和全基因组测序（WGS）的结果强调了II型钙粘蛋白是自闭症谱系障碍（ASD）的风险基因。为了确定这些钙粘蛋白是否可能与ASD相关脑区的形态发生有关，进行了原位杂交（ISH）实验，以检查发育中的小脑中两个与ASD相关的钙粘蛋白Cdh9和Cdh11的mRNA表达谱。在出生后的第一周，小脑浦肯野细胞的分离亚群中Cdh9和Cdh11均高水平表达，并且随着发育的进行，这两个基因的表达均下降。 Cdh11的发育表达主要限于ver背的小叶（小叶VI / VII）以及相当于人脑中Crus I和Crus II区域的外侧半球区域，已知这些区域可介导成年人的高级认知功能。此外，在the小叶VI / VII中，Cdh9和Cdh11以互补的模式表达，Cdh11表达区与Cdh9表达区侧接。有趣的是，小叶VI / VII中央结构域中Cdh11的高表达与Purkinje细胞标志物calbindin的低表达有关，这与Purkinje细胞在同一区域的成熟延迟有关。这些发现表明，这两个与ASD相关的钙黏着蛋白可能发挥独特但协调的功能来调节小脑中与ASD相关的电路的布线。电子补充材料本文的在线版本（10.1186 / s13041-019-0461-4）包含补充资料，可供授权用户使用。

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