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Proliferation and Differentiation of Neural Stem Cells Are Selectively Regulated by Knockout of Cyclin D1

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Abstract

Although stem cells can proliferate and differentiate through the completion of cell cycle progression, little is known about the genes and molecular mechanisms controlling this process. Here, we investigated the effect of the inhibition of cell cycle by cyclin D1 gene knockout on proliferation and differentiation of neural stem cells (NSCs). Knockout of cyclin D1 induced the cultured neural stem cells arrested at the G0/G1 phase as detected by flow cytometry. Cyclin D1 knockout led to the apoptosis of NSCs and inhibited the differentiation into astrocytes without affecting the differentiation into neurons. We further demonstrated that a significant reduction of BrdU+ cells in the subgranular zone of the dentate gyrus and subventricular zone was found in cyclin D1 gene knockout (cyclin D1−/−) mice compared with cyclin D1+/+ and cyclin D1+/− mice. These observations demonstrated that cyclin D1 plays essential roles in the proliferation and differentiation of neural stem cells.

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Abbreviations

BrdU:

5-Bromo-2′-deoxyuridine

TuJI:

β-Tubulin III

NSC:

Neural stem cell

PI:

Propidium iodide

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick-end labeling

SVZ:

The subventricular zone

DG:

The subgranular zone of the dentate gyrus

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (nos. 30725019, 30971007, and 30800341).

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Authors and Affiliations

  1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Junfang Ma, Zhiyuan Yu, Wensheng Qu, Yingxin Tang, Yan Zhan, Can Ding, Wei Wang & Minjie Xie

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  1. Junfang Ma
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  2. Zhiyuan Yu
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  3. Wensheng Qu
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  4. Yingxin Tang
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  5. Yan Zhan
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  6. Can Ding
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  7. Wei Wang
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  8. Minjie Xie
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Corresponding authors

Correspondence to Wei Wang or Minjie Xie.

Additional information

Ma J and Yu Z contribute equally to this work.

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Ma, J., Yu, Z., Qu, W. et al. Proliferation and Differentiation of Neural Stem Cells Are Selectively Regulated by Knockout of Cyclin D1. J Mol Neurosci 42, 35–43 (2010). https://doi.org/10.1007/s12031-010-9362-9

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  • DOI: https://doi.org/10.1007/s12031-010-9362-9

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