Cited 87 times in
An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development
DC Field | Value | Language |
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dc.contributor.author | 강훈철 | - |
dc.contributor.author | 김상우 | - |
dc.date.accessioned | 2018-03-26T16:52:30Z | - |
dc.date.available | 2018-03-26T16:52:30Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/156904 | - |
dc.description.abstract | Focal malformations of cortical development (FMCDs) account for the majority of drug-resistant pediatric epilepsy. Postzygotic somatic mutations activating the phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway are found in a wide range of brain diseases, including FMCDs. It remains unclear how a mutation in a small fraction of cells disrupts the architecture of the entire hemisphere. Within human FMCD-affected brain, we found that cells showing activation of the PI3K-AKT-mTOR pathway were enriched for the AKT3(E17K) mutation. Introducing the FMCD-causing mutation into mouse brain resulted in electrographic seizures and impaired hemispheric architecture. Mutation-expressing neural progenitors showed misexpression of reelin, which led to a non-cell autonomous migration defect in neighboring cells, due at least in part to derepression of reelin transcription in a manner dependent on the forkhead box (FOX) transcription factor FOXG1. Treatments aimed at either blocking downstream AKT signaling or inactivating reelin restored migration. These findings suggest a central AKT-FOXG1-reelin signaling pathway in FMCD and support pathway inhibitors as potential treatments or therapies for some forms of focal epilepsy. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Nature Publishing Company | - |
dc.relation.isPartOf | NATURE MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Base Sequence | - |
dc.subject.MESH | Cell Adhesion Molecules, Neuronal/metabolism* | - |
dc.subject.MESH | Cell Differentiation | - |
dc.subject.MESH | Cell Movement*/genetics | - |
dc.subject.MESH | Disease Models, Animal | - |
dc.subject.MESH | Enzyme Activation | - |
dc.subject.MESH | Extracellular Matrix Proteins/metabolism* | - |
dc.subject.MESH | Forkhead Transcription Factors/metabolism* | - |
dc.subject.MESH | Gene Expression Regulation, Developmental | - |
dc.subject.MESH | Gene Regulatory Networks | - |
dc.subject.MESH | Green Fluorescent Proteins/metabolism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Magnetic Resonance Imaging | - |
dc.subject.MESH | Malformations of Cortical Development/enzymology | - |
dc.subject.MESH | Malformations of Cortical Development/metabolism* | - |
dc.subject.MESH | Malformations of Cortical Development/pathology* | - |
dc.subject.MESH | Malformations of Cortical Development/surgery | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Molecular Sequence Data | - |
dc.subject.MESH | Mosaicism | - |
dc.subject.MESH | Mutation/genetics | - |
dc.subject.MESH | Nerve Tissue Proteins/metabolism* | - |
dc.subject.MESH | Neural Stem Cells/metabolism | - |
dc.subject.MESH | Neurons/metabolism | - |
dc.subject.MESH | Neurons/pathology | - |
dc.subject.MESH | Phenotype | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt/metabolism* | - |
dc.subject.MESH | RNA, Small Interfering/metabolism | - |
dc.subject.MESH | Real-Time Polymerase Chain Reaction | - |
dc.subject.MESH | Recombination, Genetic/genetics | - |
dc.subject.MESH | Serine Endopeptidases/metabolism* | - |
dc.subject.MESH | Signal Transduction/genetics | - |
dc.subject.MESH | TOR Serine-Threonine Kinases/metabolism | - |
dc.title | An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Pediatrics | - |
dc.contributor.googleauthor | Seung Tae Baek | - |
dc.contributor.googleauthor | Brett Copeland | - |
dc.contributor.googleauthor | Eun-Jin Yun | - |
dc.contributor.googleauthor | Seok-Kyu Kwon | - |
dc.contributor.googleauthor | Alicia Guemez-Gamboa | - |
dc.contributor.googleauthor | Ashleigh E. Schaffer | - |
dc.contributor.googleauthor | Sangwoo Kim | - |
dc.contributor.googleauthor | Hoon-Chul Kang | - |
dc.contributor.googleauthor | Saera Song | - |
dc.contributor.googleauthor | Gary W. Mathern | - |
dc.contributor.googleauthor | Joseph G. Gleeson | - |
dc.identifier.doi | 10.1038/nm.3982 | - |
dc.contributor.localId | A00102 | - |
dc.contributor.localId | A00524 | - |
dc.relation.journalcode | J02296 | - |
dc.identifier.eissn | 1546-170X | - |
dc.identifier.pmid | 26523971 | - |
dc.subject.keyword | Postzygotic | - |
dc.subject.keyword | somatic mosaic | - |
dc.subject.keyword | neuropsychiatric | - |
dc.subject.keyword | seizures | - |
dc.subject.keyword | epilepsy | - |
dc.subject.keyword | AKT | - |
dc.subject.keyword | PI3K | - |
dc.subject.keyword | MTOR | - |
dc.subject.keyword | malformations of cortical development | - |
dc.contributor.alternativeName | Kang, Hoon Chul | - |
dc.contributor.alternativeName | Kim, Sang Woo | - |
dc.contributor.affiliatedAuthor | Kang, Hoon Chul | - |
dc.contributor.affiliatedAuthor | Kim, Sang Woo | - |
dc.citation.volume | 21 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1445 | - |
dc.citation.endPage | 1454 | - |
dc.identifier.bibliographicCitation | NATURE MEDICINE, Vol.21(12) : 1445-1454, 2015 | - |
dc.identifier.rimsid | 41213 | - |
dc.type.rims | ART | - |
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