2. Academic Validation
  3. The Primate-Specific Gene TMEM14B Marks Outer Radial Glia Cells and Promotes Cortical Expansion and Folding

The Primate-Specific Gene TMEM14B Marks Outer Radial Glia Cells and Promotes Cortical Expansion and Folding

  • Cell Stem Cell. 2017 Nov 2;21(5):635-649.e8. doi: 10.1016/j.stem.2017.08.013.
Jing Liu 1,  Wensu Liu 1,  Lu Yang 2,  Qian Wu 3,  Haofeng Zhang 4,  Ai Fang 1,  Long Li 1,  Xiaohui Xu 4,  Le Sun 3,  Jun Zhang 5,  Fuchou Tang 6,  Xiaoqun Wang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 BIOPIC, ICG, School of Life Sciences, Peking University, Beijing 100871, China.
  • 3 State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 Obstetrics and Gynecology Medical Center of Severe Cardiovascular Disease of Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
  • 5 Obstetrics and Gynecology Medical Center of Severe Cardiovascular Disease of Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address: drzhangj@outlook.com.
  • 6 BIOPIC, ICG, School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: tangfuchou@pku.edu.cn.
  • 7 State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Brain Disorders, Beijing 100069, China. Electronic address: xiaoqunwang@ibp.ac.cn.
PMID: 29033352 DOI: 10.1016/j.stem.2017.08.013
Abstract

Human brain evolution is associated with expansion and folding of the neocortex. Increased diversity in neural progenitor (NP) populations (such as basally located radial glia [RG], which reside in an enlarged outer subventricular zone [OSVZ]) likely contributes to this evolutionary expansion, although their characteristics and relative contributions are only partially understood. Through single-cell transcriptional profiling of sorted human NP subpopulations, we identified the primate-specific TMEM14B gene as a marker of basal RG. Expression of TMEM14B in embryonic NPs induces cortical thickening and gyrification in postnatal mice. This is accompanied by SVZ expansion, the appearance of outer RG-like cells, and the proliferation of multiple NP subsets, with proportional increases in all cortical layers and normal lamination. TMEM14B drives NP proliferation by increasing the phosphorylation and nuclear translocation of IQGAP1, which in turn promotes G1/S cell cycle transitions. These data show that a single primate-specific gene can drive neurodevelopmental changes that contribute to brain evolution.

Keywords

IQGAP1; TMEM14B; basal radial glia; gyrification; human neocortex; intermediate progenitor; neural progenitor; neurogenesis; outer radial glia; radial glia.

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