The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain dev...

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Main Authors: Xiang-Chun Ju, Qiong-Qiong Hou, Ai-Li Sheng, Kong-Yan Wu, Yang Zhou, Ying Jin, Tieqiao Wen, Zhengang Yang, Xiaoqun Wang, Zhen-Ge Luo
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2016-08-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/18197
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author Xiang-Chun Ju
Qiong-Qiong Hou
Ai-Li Sheng
Kong-Yan Wu
Yang Zhou
Ying Jin
Tieqiao Wen
Zhengang Yang
Xiaoqun Wang
Zhen-Ge Luo
author_facet Xiang-Chun Ju
Qiong-Qiong Hou
Ai-Li Sheng
Kong-Yan Wu
Yang Zhou
Ying Jin
Tieqiao Wen
Zhengang Yang
Xiaoqun Wang
Zhen-Ge Luo
author_sort Xiang-Chun Ju
collection DOAJ
description Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding.
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spelling doaj.art-85954edf19c042f9a1c4a7d4e15097922022-12-22T03:51:18ZengeLife Sciences Publications LtdeLife2050-084X2016-08-01510.7554/eLife.18197The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in miceXiang-Chun Ju0Qiong-Qiong Hou1Ai-Li Sheng2Kong-Yan Wu3Yang Zhou4Ying Jin5Tieqiao Wen6Zhengang Yang7Xiaoqun Wang8Zhen-Ge Luo9https://orcid.org/0000-0001-5037-0542Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, China; Chinese Academy of Sciences University, Beijing, ChinaInstitute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, China; Chinese Academy of Sciences University, Beijing, ChinaInstitute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, ChinaInstitute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, ChinaThe Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, ChinaThe Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaInstitutes of Brain Science, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, ChinaCAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China; Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaInstitute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, China; Chinese Academy of Sciences University, Beijing, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China; ShanghaiTech University, Shanghai, ChinaCortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding.https://elifesciences.org/articles/18197neural progenitorscortical foldinghominoid-specific gene
spellingShingle Xiang-Chun Ju
Qiong-Qiong Hou
Ai-Li Sheng
Kong-Yan Wu
Yang Zhou
Ying Jin
Tieqiao Wen
Zhengang Yang
Xiaoqun Wang
Zhen-Ge Luo
The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
eLife
neural progenitors
cortical folding
hominoid-specific gene
title The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
title_full The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
title_fullStr The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
title_full_unstemmed The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
title_short The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
title_sort hominoid specific gene tbc1d3 promotes generation of basal neural progenitors and induces cortical folding in mice
topic neural progenitors
cortical folding
hominoid-specific gene
url https://elifesciences.org/articles/18197
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