Autism-associated ANK2 regulates embryonic neurodevelopment
Autism-associated ANK2 regulates embryonic neurodevelopment
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DOI：
10.1016/j.bbrc.2022.03.058
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发表时间：
2022-05-21
影响因子：
3.1
通讯作者：
Nakazawa, Takanobu
中科院分区：
文献类型：
--
作者：
Kawano, Shotaro;Baba, Masayuki;Nakazawa, Takanobu
自闭症谱系障碍（ASD）是一种神经发育状况，其特征是社会交往改变，兴趣受限和刻板行为。虽然ASD的分子和细胞发病机制仍然难以捉摸，受损的神经干细胞分化和皮质发育过程中的神经元迁移被认为是关键参与ASD。ANK2编码一种细胞骨架支架蛋白，参与将膜蛋白募集到专门的膜结构域中，已被鉴定为高置信度ASD风险基因。然而，ANK2在早期神经发育中的作用仍不清楚。在本研究中，我们利用子宫内电穿孔技术分析了ANK2在发育中的小鼠大脑皮层中的作用。我们提供的证据表明，ANK2调节神经干细胞分化和神经元迁移的胚胎大脑皮层，其中ANK2是高度表达。我们还证明了Ank2敲低改变了参与神经发育的基因的表达。总之，这些结果支持ANK2单倍不足可能损害神经发育，导致ASD风险增加的观点。我们的研究结果为ASD的分子和细胞发病机制提供了新的见解，因为在高置信度的ASD基因中，ANK2是罕见的，因为它编码神经元功能所需的膜蛋白复合物的支架蛋白。(C)2022年，任作家。爱思唯尔公司出版
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by altered social communication, restricted interests, and stereotypic behaviors. Although the molecular and cellular pathogeneses of ASD remain elusive, impaired neural stem cell differentiation and neuronal migration during cortical development are suggested to be critically involved in ASD. ANK2, which encodes for a cytoskeletal scaffolding protein involved in recruiting membrane proteins into specialized membrane domains, has been identified as a high-confidence ASD risk gene. However, the role of ANK2 in early neural development remains unclear. In this study, we analyzed the role of ANK2 in the cerebral cortex of developing mouse using in utero electroporation. We provide evidence suggesting that ANK2 regulates neural stem cell differentiation and neuronal migration in the embryonic cerebral cortex, where Ank2 is highly expressed. We also demonstrated that Ank2 knockdown alters the expression of genes involved in neural development. Taken together, these results support the view that ANK2 haploinsufficiency in patients may impair neural development, resulting in an increased risk of ASD. Our study findings provide new insights into the molecular and cellular pathogenesis of ASD, given that among high-confidence ASD genes, ANK2 is rare in that it encodes for a scaffolding protein for the membrane protein complex required for neuronal functions. (C) 2022 The Authors. Published by Elsevier Inc.