The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
- Chinese Academy of Sciences, China
- Shanghai University, China
- Fudan University, China
- CAS Center for Excellence in Brain Science and Intelligence Technology, China
Abstract
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 it's 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 promotes 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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Funding
Ministry of Science and Technology of the People's Republic of China (2014CB910203)
- Zhen-Ge Luo
National Natural Science Foundation of China (31330032)
- Zhen-Ge Luo
National Natural Science Foundation of China (31490591)
- Zhen-Ge Luo
National Natural Science Foundation of China (31321091)
- Zhen-Ge Luo
National Natural Science Foundation of China (61327902)
- Zhen-Ge Luo
Chinese Academy of Sciences (XDB02040003)
- Zhen-Ge Luo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (8th Edition, 2010). All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#NA-008-2016) of the Institute of Neuroscience, Chinese Academy of Sciences. All surgery was performed under anesthesia with pentobarbital sodium, and every effort was made to minimize suffering.
Human subjects: Human fetal brain tissue samples were collected at autopsy within 3 hr of spontaneous abortion with the informed consent of the patients following protocols and institutional ethic guidelines approved by ethics committee of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (Approval identifier number: ER-SIBS-221506). Brain tissues were stored in ice-cold Leibowitz-15 medium and transported to the laboratory for further examination and processing.
Copyright
© 2016, Ju et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
eLife 5:e18197.
https://doi.org/10.7554/eLife.18197
