Loss of Lgl1 Disrupts the Radial Glial Fiber-guided Cortical Neuronal Migration and Causes Subcortical Band Heterotopia in Mice
Loss of Lgl1 Disrupts the Radial Glial Fiber-guided Cortical Neuronal Migration and Causes Subcortical Band Heterotopia in Mice
复制标题
Lgl1 的缺失会破坏径向胶质纤维引导的皮质神经元迁移并导致小鼠皮质下带异位
DOI：
10.1016/j.neuroscience.2018.12.039
复制
发表时间：
2019-02
期刊：
影响因子：
3.3
通讯作者：
Gao Jiangang
中科院分区：
文献类型：
--
作者：
Zhang Tingting;Zhang Sen;Song Xinli;Zhao Xiaohan;Hou Congzhe;Li Zhenzu;Gao Jiangang
放射状胶质细胞（RGC）是神经元的祖细胞，在发育中的大脑皮层中充当神经元放射状迁移的支架。这些功能依赖于极化的放射状胶质支架，这对大脑发育至关重要。致死性巨幼虫1（Lgl 1）是果蝇哺乳动物细胞极性的关键调节因子，在肿瘤发生和脑发育中起重要作用。为了克服Lgl 1基因敲除小鼠的新生儿致死性，并阐明Lgl 1在小鼠大脑皮层发育和功能中的作用，我们建立了Emx 1-Cre介导的Lgl 1背侧端脑特异性基因敲除小鼠。Lgl 1 Emx 1条件性基因敲除（CKO）小鼠寿命正常，可用于功能研究。组织学结果显示，突变小鼠在正常运动皮质和皮质下白色物质之间的背外侧半球区域显示异位皮质团块，类似于人类皮质下带状异位（SBH）。Lgl 1 Emx 1CKO皮质显示破坏的粘附连接（AJs），伴随着异位RGCs和中间祖细胞，以及放射状胶质纤维系统的解体。早期和晚期出生的神经元未能沿着断裂的放射状胶质纤维支架沿着到达预定位置，而是在异位位置积聚并形成SBH。此外，Lgl 1的缺乏导致RGCs的严重异常，包括过度增殖、分化受损和凋亡增加。Lgl 1 Emx 1CKO小鼠也表现出焦虑相关行为的缺陷。我们的结论是，Lgl 1是必不可少的RGC的发展和大脑皮层发育过程中的神经迁移。
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 fromDrosophilato 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. Lgl1Emx1conditional 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 Lgl1Emx1CKO 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. Lgl1Emx1CKO mice also displayed deficiencies in anxiety-related behaviors. We concluded that Lgl1 is essential for RGC development and neural migration during cerebral cortex development.
登录
查看更多内容
影响因子：
2.9
作者：
Hideaki Yamamoto;K. Mandai;D. Konno;T. Maruo;F. Matsuzaki;Y. Takai
通讯作者：
Hideaki Yamamoto;K. Mandai;D. Konno;T. Maruo;F. Matsuzaki;Y. Takai
影响因子：
5.3
作者：
DArcangelo, G;Nakajima, K;Curran, T
通讯作者：
Curran, T
影响因子：
2.7
作者：
Hutton, Scott R.;Pevny, Larysa H.
通讯作者：
Pevny, Larysa H.
影响因子：
21.3
作者：
Plant, PJ;Fawcett, JP;Pawson, T
通讯作者：
Pawson, T
影响因子：
3.2
作者：
S. Ravid
通讯作者：
S. Ravid