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Elife. 2016 Aug 9;5. pii: e18197. doi: 10.7554/eLife.18197.

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

Ju XC1,2,3, Hou QQ1,2,3, Sheng AL1,2, Wu KY1,2, Zhou Y4, Jin Y4, Wen T5, Yang Z6, Wang X7,8, Luo ZG1,2,3,7,9.

Author information

1
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
2
State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, China.
3
Chinese Academy of Sciences University, Beijing, China.
4
The Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
5
School of Life Sciences, Shanghai University, Shanghai, China.
6
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
7
CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China.
8
Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
9
ShanghaiTech University, Shanghai, 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 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.

KEYWORDS:

cortical folding; hominoid-specific gene; mouse; neural progenitors; neuroscience

PMID:
27504805
PMCID:
PMC5028191
DOI:
10.7554/eLife.18197
[Indexed for MEDLINE]
Free PMC Article

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