Open AccessLgl1 deficiency disrupts hippocampal development and impairs cognitive performance in mice
Author(s) -
Zhang Tingting,
Hou Congzhe,
Zhang Sen,
Liu Shuoyang,
Li Zhenzu,
Gao Jiangang
Publication year - 2019
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12605
Subject(s) - hippocampal formation , hippocampus , neuroscience , olfactory bulb , embryonic stem cell , microbiology and biotechnology , biology , central nervous system , biochemistry , gene
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.