title: Essential roles of leucine-rich glioma inactivated 1 in the development of embryonic and postnatal cerebellum.
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.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Xie
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Physiology and Pharmacology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Nanwei
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zou
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Georgia Regents University, Cancer Center, Augusta, GA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Cowell
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism*; D063928:Ependymoglial Cells / Q000166:cytology / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D064231:Nestin / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; C492120:Lgi1 protein, mouse; D064231:Nestin; D011506:Proteins; D051880:Receptors, Notch