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

  1. Xiang-Chun Ju
  2. Qiong-Qiong Hou
  3. Ai-Li Sheng Sheng
  4. Kong-Yan Wu
  5. Yang Zhou
  6. Ying Jin
  7. Tieqiao Wen
  8. Zhengang Yang
  9. Xiaoqun Wang
  10. Zhen-Ge Luo  Is a corresponding author
  1. Chinese Academy of Sciences, China
  2. Shanghai University, China
  3. Fudan University, China
  4. 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.

Article and author information

Author details

  1. Xiang-Chun Ju

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Qiong-Qiong Hou

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Ai-Li Sheng Sheng

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Kong-Yan Wu

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yang Zhou

    The Institute of Health Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Ying Jin

    The Institute of Health Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Tieqiao Wen

    School of Life Sciences, Shanghai University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Zhengang Yang

    Institutes of Brain Science, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Xiaoqun Wang

    CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Zhen-Ge Luo

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    zgluo@ion.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5037-0542

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.

Metrics

  • 5,345
    views
  • 1,260
    downloads
  • 143
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Xiang-Chun Ju
  2. Qiong-Qiong Hou
  3. Ai-Li Sheng Sheng
  4. Kong-Yan Wu
  5. Yang Zhou
  6. Ying Jin
  7. Tieqiao Wen
  8. Zhengang Yang
  9. Xiaoqun Wang
  10. Zhen-Ge Luo
(2016)
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

Share this article

https://doi.org/10.7554/eLife.18197

Further reading

    1. Neuroscience
    Yafen Li, Yixuan Lin ... Antao Chen
    Research Article

    Concurrent verbal working memory task can eliminate the color-word Stroop effect. Previous research, based on specific and limited resources, suggested that the disappearance of the conflict effect was due to the memory information preempting the resources for distractors. However, it remains unclear which particular stage of Stroop conflict processing is influenced by working memory loads. In this study, electroencephalography (EEG) recordings with event-related potential (ERP) analyses, time-frequency analyses, multivariate pattern analyses (MVPAs), and representational similarity analyses (RSAs) were applied to provide an in-depth investigation of the aforementioned issue. Subjects were required to complete the single task (the classical manual color-word Stroop task) and the dual task (the Sternberg working memory task combined with the Stroop task), respectively. Behaviorally, the results indicated that the Stroop effect was eliminated in the dual-task condition. The EEG results showed that the concurrent working memory task did not modulate the P1, N450, and alpha bands. However, it modulated the sustained potential (SP), late theta (740–820 ms), and beta (920–1040 ms) power, showing no difference between congruent and incongruent trials in the dual-task condition but significant difference in the single-task condition. Importantly, the RSA results revealed that the neural activation pattern of the late theta was similar to the response interaction pattern. Together, these findings implied that the concurrent working memory task eliminated the Stroop effect through disrupting stimulus-response mapping.

    1. Evolutionary Biology
    2. Neuroscience
    Anastasia A Makarova, Nicholas J Chua ... Alexey A Polilov
    Research Article

    The structure of compound eyes in arthropods has been the subject of many studies, revealing important biological principles. Until recently, these studies were constrained by the two-dimensional nature of available ultrastructural data. By taking advantage of the novel three-dimensional ultrastructural dataset obtained using volume electron microscopy, we present the first cellular-level reconstruction of the whole compound eye of an insect, the miniaturized parasitoid wasp Megaphragma viggianii. The compound eye of the female M. viggianii consists of 29 ommatidia and contains 478 cells. Despite the almost anucleate brain, all cells of the compound eye contain nuclei. As in larger insects, the dorsal rim area of the eye in M. viggianii contains ommatidia that are believed to be specialized in polarized light detection as reflected in their corneal and retinal morphology. We report the presence of three ‘ectopic’ photoreceptors. Our results offer new insights into the miniaturization of compound eyes and scaling of sensory organs in general.