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

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 differentiat...

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Autores principales:	Jiheon Shin, Minhyung Kim, Hee-Jung Jung, Hye Lim Cha, Haeyoung Suh-Kim, Sanghyun Ahn, Jaehoon Jung, YounAh Kim, Yukyung Jun, Sanghyuk Lee, Daehee Hwang, Jaesang Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe088a2c590c43dc9c31e7ab01885183
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spelling	oai:doaj.org-article:fe088a2c590c43dc9c31e7ab018851832021-12-02T11:53:08ZCharacterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data10.1038/s41598-017-02842-62045-2322https://doaj.org/article/fe088a2c590c43dc9c31e7ab018851832017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02842-6https://doaj.org/toc/2045-2322Abstract 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.Jiheon ShinMinhyung KimHee-Jung JungHye Lim ChaHaeyoung Suh-KimSanghyun AhnJaehoon JungYounAh KimYukyung JunSanghyuk LeeDaehee HwangJaesang KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiheon Shin Minhyung Kim Hee-Jung Jung Hye Lim Cha Haeyoung Suh-Kim Sanghyun Ahn Jaehoon Jung YounAh Kim Yukyung Jun Sanghyuk Lee Daehee Hwang Jaesang Kim Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data
description	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.
format	article
author	Jiheon Shin Minhyung Kim Hee-Jung Jung Hye Lim Cha Haeyoung Suh-Kim Sanghyun Ahn Jaehoon Jung YounAh Kim Yukyung Jun Sanghyuk Lee Daehee Hwang Jaesang Kim
author_facet	Jiheon Shin Minhyung Kim Hee-Jung Jung Hye Lim Cha Haeyoung Suh-Kim Sanghyun Ahn Jaehoon Jung YounAh Kim Yukyung Jun Sanghyuk Lee Daehee Hwang Jaesang Kim
author_sort	Jiheon Shin
title	Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data
title_short	Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data
title_full	Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data
title_fullStr	Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data
title_full_unstemmed	Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data
title_sort	characterization of developmental defects in the forebrain resulting from hyperactivated mtor signaling by integrative analysis of transcriptomic and proteomic data
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fe088a2c590c43dc9c31e7ab01885183
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Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data

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