DC Field | Value | Language |
---|---|---|
dc.contributor.author | YUN, EUN JIN | - |
dc.contributor.author | BAEK, SEUNG TAE | - |
dc.contributor.author | Copeland B | - |
dc.contributor.author | Kwon SK | - |
dc.contributor.author | Guemez-Gamboa A | - |
dc.contributor.author | Schaffer AE | - |
dc.contributor.author | Kim S | - |
dc.contributor.author | Kang HC | - |
dc.contributor.author | Song S | - |
dc.contributor.author | Mathern GW | - |
dc.contributor.author | Gleeson JG | - |
dc.date.accessioned | 2018-01-04T12:27:54Z | - |
dc.date.available | 2018-01-04T12:27:54Z | - |
dc.date.created | 2017-11-13 | - |
dc.date.issued | 2015-12 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/39307 | - |
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.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.relation.isPartOf | NATURE MEDICINE | - |
dc.title | An AKT3-FOXG1-Reelin network underlies defective migration in human focal malformations of cortical development | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/nm.3982 | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | NATURE MEDICINE, v.21, no.12, pp.1445 - + | - |
dc.identifier.wosid | 000366008700015 | - |
dc.date.tcdate | 2019-02-01 | - |
dc.citation.endPage | + | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1445 | - |
dc.citation.title | NATURE MEDICINE | - |
dc.citation.volume | 21 | - |
dc.contributor.affiliatedAuthor | YUN, EUN JIN | - |
dc.contributor.affiliatedAuthor | BAEK, SEUNG TAE | - |
dc.identifier.scopusid | 2-s2.0-84949564339 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.wostc | 34 | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | CONTROL NEURONAL MIGRATION | - |
dc.subject.keywordPlus | LHERMITTE-DUCLOS-DISEASE | - |
dc.subject.keywordPlus | COPY-NUMBER VARIATION | - |
dc.subject.keywordPlus | SOMATIC MUTATIONS | - |
dc.subject.keywordPlus | CEREBRAL-CORTEX | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR | - |
dc.subject.keywordPlus | DEVELOPING NEOCORTEX | - |
dc.subject.keywordPlus | PIK3CA CAUSE | - |
dc.subject.keywordPlus | HUMAN BRAIN | - |
dc.subject.keywordPlus | REELIN | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
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