Developmental disruptions underlying brain abnormalities in ciliopathies.
Developmental disruptions underlying brain abnormalities in ciliopathies.
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DOI：
10.1038/ncomms8857
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发表时间：
2015-07-24
影响因子：
16.6
通讯作者：
Anton ES
中科院分区：
文献类型：
--
作者：
Guo J;Higginbotham H;Li J;Nichols J;Hirt J;Ghukasyan V;Anton ES
初级纤毛是构成主要细胞功能的重要信号传送器。大脑皮层前体细胞和神经元具有初级纤毛。纤毛功能对大脑发育和功能的重要性在与人类纤毛疾病相关的大量发育性大脑疾病中是显而易见的。然而，初级纤毛功能在皮质生成中的作用仍然很大程度上是未知的。在这里，我们利用针对纤毛病基因的shRNA文库描述了初级纤毛在大脑皮层结构中的功能及其与纤毛疾病的相关性，该基因可导致大脑疾病，但其在大脑发育中的作用尚不清楚。我们使用该文库来查询纤毛病变基因如何影响小鼠皮质发育的不同阶段，特别是神经前体发育、神经元迁移、神经元分化和早期神经元连接。我们的结果定义了纤毛病变基因的发育功能，并描绘了与纤毛病变中脑异常的出现密切相关的发育中断事件。初级纤毛是主要细胞功能的基本信号传送器，但它们在大脑发育中的作用尚不完全清楚。在这里，作者编辑了一个针对纤毛病变基因的shRNA文库，已知的纤毛病变基因会导致大脑紊乱，并用它来询问纤毛病变基因如何影响小鼠皮质发育的不同阶段。
Primary cilia are essential conveyors of signals underlying major cell functions. Cerebral cortical progenitors and neurons have a primary cilium. The significance of cilia function for brain development and function is evident in the plethora of developmental brain disorders associated with human ciliopathies. Nevertheless, the role of primary cilia function in corticogenesis remains largely unknown. Here we delineate the functions of primary cilia in the construction of cerebral cortex and their relevance to ciliopathies, using an shRNA library targeting ciliopathy genes known to cause brain disorders, but whose roles in brain development are unclear. We used the library to query how ciliopathy genes affect distinct stages of mouse cortical development, in particular neural progenitor development, neuronal migration, neuronal differentiation and early neuronal connectivity. Our results define the developmental functions of ciliopathy genes and delineate disrupted developmental events that are integrally related to the emergence of brain abnormalities in ciliopathies. Primary cilia are essential conveyors of signals underlying major cellular functions but their role in brain development is not completely understood. Here the authors compiled a shRNA library targeting ciliopathy genes known to cause brain disorders, and used it to query how ciliopathy genes affect distinct stages of mouse cortical development.