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Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data

Title
Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data
Authors
Shin, JiheonKim, MinhyungJung, Hee-JungCha, Hye LimSuh-Kim, HaeyoungAhn, SanghyunJung, JaehoonKim, YounAhJun, YukyungLee, SanghyukHwang, DaeheeKim, Jaesang
DGIST Authors
Jung, Hee-Jung; Ahn, Sanghyun; Kim, YounAh; Hwang, Daehee
Issue Date
2017-06-06
Citation
Scientific Reports, 7
Type
Article
Article Type
Article
Keywords
CancerInteraction NetworksMass Spectrometric DataMutationsPathwaysProteinsProteogenomic CharacterizationRefinementRevealsTuberous Sclerosis Complex
ISSN
2045-2322
Abstract
Hyperactivated mTOR signaling in the developing brain has been implicated in multiple forms of pathology including tuberous sclerosis complex (TSC). To date, various phenotypic defects such as cortical lamination irregularity, subependymal nodule formation, dysmorphic astrocyte differentiation and dendritic malformation have been described for patients and animal models. However, downstream networks affected in the developing brain by hyperactivated mTOR signaling have yet to be characterized. Here, we present an integrated analysis of transcriptomes and proteomes generated from wild-type and Tsc1/Emx1-Cre forebrains. This led to comprehensive lists of genes and proteins whose expression levels were altered by hyperactivated mTOR signaling. Further incorporation of TSC patient data followed by functional enrichment and network analyses pointed to changes in molecular components and cellular processes associated with neuronal differentiation and morphogenesis as the key downstream events underlying developmental and morphological defects in TSC. Our results provide novel and fundamental molecular bases for understanding hyperactivated mTOR signaling-induced brain defects which can in turn facilitate identification of potential diagnostic markers and therapeutic targets for mTOR signaling-related neurological disorders. © The Author(s) 2017.
URI
http://hdl.handle.net/20.500.11750/4154
DOI
10.1038/s41598-017-02842-6
Publisher
Nature Publishing Group
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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Collection:
New BiologyETC1. Journal Articles
ETC1. Journal Articles


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