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- Title
Essential roles of leucine-rich glioma inactivated 1 in the development of embryonic and postnatal cerebellum.
- Authors
Zhou, Liang; Zou, Na; Jiang, Nanwei; Xie, Ya-Jun; Zhou, Lin; Cowell, John K.; Shen, Ying; Zhang, Nan; Wang, Yin
- Abstract
Leucine-rich glioma inactivated 1 (LGI1) is a secreted protein that interacts with ADAM transmembrane proteins, and its mutations are linked to human epilepsy. The function of LGI1 in CNS development remains undefined. Here, we report novel functions of LGI1 in the generation of cerebellar granule precursors (CGPs) and differentiation of radial glial cells (RGCs) in the cerebellum. A reduction in external granule layer thickness and defects in foliation were seen in embryonic and new-born LGI1 knockout (KO) mice. BrdU staining showed an inhibited proliferation of CGPs in KO embryos, which might be explained by the reduced Sonic hedgehog in embryos. In addition, the differentiation of RGCs into Bergmann glias was suppressed in KO mice. Enhanced Jagged1-Notch1 signaling in KO mice via reduced β-secretase proteolysis suggests that altered phenotype of RGCs is due to abnormal Notch1 signaling. Together, our results demonstrate that LGI1 is an essential player in the cerebellar development.
- Subjects
GLIOMAS; CEREBRAL cortex development; DEVELOPMENTAL biology; EMBRYOLOGY; NEUROGLIA; KNOCKOUT mice
- Publication
Scientific Reports, 2015, p7827
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep07827