Abstract
The generation of specialized neural cells in the developing and postnatal central nervous system is a highly regulated process, whereby neural stem cells divide to generate committed neuronal progenitors, which then withdraw from the cell cycle and start to differentiate. Cell cycle checkpoints play a major role in regulating the balance between neural stem cell expansion and differentiation. Loss of tumor suppressors involved in checkpoint control can lead to dramatic alterations of neurogenesis, thus contributing to neoplastic transformation. Here we summarize and critically discuss the existing literature on the role of tumor suppressive pathways and their regulatory networks in the control of neurogenesis and transformation.
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Acknowledgments
We would like to acknowledge members of the PS lab for critical discussion. PS is supported by the Samantha Dickson Brain Tumour Trust (SDBTT). Special thanks are due to the Brian Cross family for their generous support of the Samantha Dickson Brain Cancer Unit. SB is supported by the SDBTT. We also thank David Hunter and Wendy Tansey for a generous donation in memory of Peter Clark.
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Glossary
Glossary
- Neural stem cells (NSCs):
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Neural stem cells are the self-renewing, multi-potent stem cells of the nervous system. Neural stem cells have the potential to give rise to offspring cells that grow and differentiate in neurons and glia cells.
- Transit amplifying cells:
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Transit amplifying cells are mitotic cells of the neural lineage with a fast dividing cell cycle that retain the ability to proliferate and to give rise to terminally differentiated cells but are not capable of indefinite self-renewal.
- Neural precursor cells (NPCs):
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Neural precursor cells (NPCs) general term to identify any neural stem or progenitor cells.
- Note:
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Controversy about the exact definition remains and the concept is still evolving [1, 26–28].
- Self-renewal:
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The process by which a stem cell divides asymmetrically or symmetrically over an extended period of time (for example, during the life-span of an animal) to generate one or two daughter stem cells that have a developmental potential similar to the mother cell. Self-renewal is used by neural stem cells to expand during development, within niche of the adult brain, and upon brain injury.
- Quiescent cell:
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A cell whose cell cycle has been temporary arrested, although, strictly speaking, it might still be cycling but with a particular long cell cycle. Note! Adult neural stem cells can be quiescent.
- Post-mitotic cells:
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A cell that is incapable of proliferation, such as a neuron, in which cell cycle is irreversibly blocked.
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Bartesaghi, S., Salomoni, P. Tumor suppressive pathways in the control of neurogenesis. Cell. Mol. Life Sci. 70, 581–597 (2013). https://doi.org/10.1007/s00018-012-1063-9
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DOI: https://doi.org/10.1007/s00018-012-1063-9