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Featured ArticleArticles, Development/Plasticity/Repair

Heterogeneously Expressed fezf2 Patterns Gradient Notch Activity in Balancing the Quiescence, Proliferation, and Differentiation of Adult Neural Stem Cells

Michael A. Berberoglu, Zhiqiang Dong, Guangnan Li, Jiashun Zheng, Luz del Carmen G. Trejo Martinez, Jisong Peng, Mahendra Wagle, Brian Reichholf, Claudia Petritsch, Hao Li, Samuel J. Pleasure and Su Guo
Journal of Neuroscience 15 October 2014, 34 (42) 13911-13923; https://doi.org/10.1523/JNEUROSCI.1976-14.2014
Michael A. Berberoglu
1Department of Bioengineering and Therapeutic Sciences,
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
3Graduate Program in Neuroscience,
4Institute of Human Genetics,
9Department of Molecular Genetics, Ohio State University, Columbus, Ohio 43210,
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Zhiqiang Dong
1Department of Bioengineering and Therapeutic Sciences,
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
4Institute of Human Genetics,
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  • ORCID record for Zhiqiang Dong
Guangnan Li
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
5Department of Neurology,
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Jiashun Zheng
6Department of Biochemistry and Biophysics,
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Luz del Carmen G. Trejo Martinez
1Department of Bioengineering and Therapeutic Sciences,
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
4Institute of Human Genetics,
11Graduate Program in Cell and Molecular Biology, Department of Biology, San Francisco State University, San Francisco, California 94132
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Jisong Peng
1Department of Bioengineering and Therapeutic Sciences,
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
4Institute of Human Genetics,
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Mahendra Wagle
1Department of Bioengineering and Therapeutic Sciences,
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
4Institute of Human Genetics,
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Brian Reichholf
7Department of Neurological Surgery, and
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Claudia Petritsch
7Department of Neurological Surgery, and
8Brain Tumor Research Center, University of California, San Francisco, California 94143-2811,
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Hao Li
6Department of Biochemistry and Biophysics,
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Samuel J. Pleasure
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
3Graduate Program in Neuroscience,
5Department of Neurology,
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Su Guo
1Department of Bioengineering and Therapeutic Sciences,
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
3Graduate Program in Neuroscience,
4Institute of Human Genetics,
10State Key Laboratory of Genetic Engineering and the Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China, and
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Abstract

Balancing quiescence, self-renewal, and differentiation in adult stem cells is critical for tissue homeostasis. The underlying mechanisms, however, remain incompletely understood. Here we identify Fezf2 as a novel regulator of fate balance in adult zebrafish dorsal telencephalic neural stem cells (NSCs). Transgenic reporters show intermingled fezf2-GFPhi quiescent and fezf2-GFPlo proliferative NSCs. Constitutive or conditional impairment of fezf2 activity demonstrates its requirement for maintaining quiescence. Analyses of genetic chimeras reveal a dose-dependent role of fezf2 in NSC activation, suggesting that the difference in fezf2 levels directionally biases fate. Single NSC profiling coupled with genetic analysis further uncovers a fezf2-dependent gradient Notch activity that is high in quiescent and low in proliferative NSCs. Finally, fezf2-GFPhi quiescent and fezf2-GFPlo proliferative NSCs are observed in postnatal mouse hippocampus, suggesting possible evolutionary conservation. Our results support a model in which fezf2 heterogeneity patterns gradient Notch activity among neighbors that is critical to balance NSC fate.

  • adult neurogenesis
  • hippocampus
  • radial glia
  • self-renewal
  • single-cell analysis
  • vivo morpholino
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The Journal of Neuroscience: 34 (42)
Journal of Neuroscience
Vol. 34, Issue 42
15 Oct 2014
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Heterogeneously Expressed fezf2 Patterns Gradient Notch Activity in Balancing the Quiescence, Proliferation, and Differentiation of Adult Neural Stem Cells
Michael A. Berberoglu, Zhiqiang Dong, Guangnan Li, Jiashun Zheng, Luz del Carmen G. Trejo Martinez, Jisong Peng, Mahendra Wagle, Brian Reichholf, Claudia Petritsch, Hao Li, Samuel J. Pleasure, Su Guo
Journal of Neuroscience 15 October 2014, 34 (42) 13911-13923; DOI: 10.1523/JNEUROSCI.1976-14.2014

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Heterogeneously Expressed fezf2 Patterns Gradient Notch Activity in Balancing the Quiescence, Proliferation, and Differentiation of Adult Neural Stem Cells
Michael A. Berberoglu, Zhiqiang Dong, Guangnan Li, Jiashun Zheng, Luz del Carmen G. Trejo Martinez, Jisong Peng, Mahendra Wagle, Brian Reichholf, Claudia Petritsch, Hao Li, Samuel J. Pleasure, Su Guo
Journal of Neuroscience 15 October 2014, 34 (42) 13911-13923; DOI: 10.1523/JNEUROSCI.1976-14.2014
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Keywords

  • adult neurogenesis
  • hippocampus
  • radial glia
  • self-renewal
  • single-cell analysis
  • vivo morpholino

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