Lgl1 deficiency disrupts hippocampal development and impairs cognitive performance in mice
Lgl1 deficiency disrupts hippocampal development and impairs cognitive performance in mice
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Lgl1 缺乏会扰乱小鼠海马发育并损害认知能力
DOI：
10.1111/gbb.12605
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发表时间：
2019-09-03
影响因子：
2.5
通讯作者：
Gao，Jiangang
中科院分区：
文献类型：
--
作者：
Zhang，Tingting;Hou，Congzhe;Gao，Jiangang
细胞极性对大脑发育和形态发生至关重要。致死巨型幼虫1 （Lethal giant幼虫1，Lgl1）在果蝇到哺乳动物细胞极性的建立过程中起着至关重要的作用。以往的研究已经发现Lgl1在小脑、嗅球和大脑皮层发育中的重要性。然而，Lgl1在胚胎期海马发育和成年小鼠的功能中的作用尚不清楚。在我们的研究中，我们用Emx1‐Cre小鼠创建了Lgl1‐缺陷海马小鼠。组织学分析表明，Emx1‐Lgl1−/−小鼠海马体积减小，海马细胞结构严重畸形。这些缺陷主要来源于海马神经上皮的破坏，包括细胞增殖增加、核相互运动迁移异常、分化减少、凋亡增加、粘附连接逐渐破坏、神经元迁移异常等。在Lgl1缺失的海马中，放射状胶质支架结构紊乱。因此，Lgl1在海马神经发生中起着独特的作用。此外，Emx1‐Lgl1−/−小鼠在Morris水迷宫和恐惧条件反射测试中表现出行为表现受损。
Cellular polarity is crucial for brain development and morphogenesis. Lethal giant larvae 1 (Lgl1) plays a crucial role in the establishment of cell polarity from Drosophila to mammalian cells. Previous studies have found the importance of Lgl1 in the development of cerebellar, olfactory bulb, and cerebral cortex. However, the role of Lgl1 in hippocampal development during the embryonic stage and function in adult mice is still unknown. In our study, we created Lgl1‐deficient hippocampus mice by using Emx1‐Cre mice. Histological analysis showed that the Emx1‐Lgl1−/− mice exhibited reduced size of the hippocampus with severe malformations of hippocampal cytoarchitecture. These defects mainly originated from the disrupted hippocampal neuroepithelium, including increased cell proliferation, abnormal interkinetic nuclear migration, reduced differentiation, increased apoptosis, gradual disruption of adherens junctions, and abnormal neuronal migration. The radial glial scaffold was disorganized in the Lgl1‐deficient hippocampus. Thus, Lgl1 plays a distinct role in hippocampal neurogenesis. In addition, the Emx1‐Lgl1−/− mice displayed impaired behavioral performance in the Morris water maze and fear conditioning test.