标题:Loss of Lgl1 Disrupts the Radial Glial Fiber-guided Cortical Neuronal Migration and Causes Subcortical Band Heterotopia in Mice
作者:Zhang, Tingting; Zhang, Sen; Song, Xinli; Zhao, Xiaohan; Hou, Congzhe; Li, Zhenzu; Gao, Jiangang
作者机构:[Zhang, Tingting; Zhang, Sen; Song, Xinli; Zhao, Xiaohan; Hou, Congzhe; Gao, Jiangang] Shandong Univ, Sch Life Sci, Jinan 250100, Shandong, Peoples R 更多
通讯作者:Gao, JG;Gao, JG;Li, ZZ
通讯作者地址:[Gao, JG]Shandong Univ, Sch Life Sci, Jinan 250100, Shandong, Peoples R China;[Gao, JG]Shandong Univ, Key Lab, Minist Educ Expt Teratol, Jinan 250100, 更多
来源:NEUROSCIENCE
出版年:2019
卷:400
页码:132-145
DOI:10.1016/j.neuroscience.2018.12.039
关键词:adherens junction; cerebral cortex; Lgl1; neuronal migration; radial; glial cells; subcortical band heterotopia
摘要:Radial glial cells (RGCs) are neuronal progenitors and function as scaffolds for neuronal radial migration in the developing cerebral cortex. These functions depend on a polarized radial glial scaffold, which is of fundamental importance for brain development. Lethal giant larvae 1 (Lgl1), a key regulator for cell polarity from Drosophila to mammals, plays a key role in tumorigenesis and brain development. To overcome neonatal lethality in Lgl1-null mice and clarify the role of Lgl1 in mouse cerebral cortex development and function, we created Lgl1 dorsal telencephalon-specific knockout mice mediated by Emx1-Cre. Lgl1(Emx1) conditional knockout (CKO) mice had normal life spans and could be used for function research. Histology results revealed that the mutant mice displayed an ectopic cortical mass in the dorsolateral hemispheric region between the normotopic cortex and the subcortical white matter, resembling human subcortical band heterotopia (SBH). The Lgl1(Emx1) CKO cortex showed disrupted adherens junctions (AJs), which were accompanied by ectopic RGCs and intermediate progenitors, and disorganization of the radial glial fiber system. The early- and late-born neurons failed to reach the destined position along the disrupted radial glial fiber scaffold and instead accumulated in ectopic positions and formed SBH. Additionally, the absence of Lgl1 led to severe abnormalities in RGCs, including hyperproliferation, impaired differentiation, and increased apoptosis. Lgl1(Emx1) CKO mice also displayed deficiencies in anxiety-related behaviors. We concluded that Lgl1 is essential for RGC development and neural migration during cerebral cortex development. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
收录类别:SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060189683&doi=10.1016%2fj.neuroscience.2018.12.039&partnerID=40&md5=691026702cc3268486e5618d9fdbf39e
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