Abstract
The control of cell fate in neural progenitor cells is critical for nervous system development. Nevertheless, the processes involved are only partially known. We found that the expression of the tumor suppressor Pml was restricted to neural progenitor cells (NPCs) in the developing neocortex of the mouse. Notably, in Pml−/− cortices, the overall number of proliferating NPCs was increased and transition between the two major progenitor types, radial glial cells and basal progenitors, was impaired. This in turn resulted in reduced differentiation and an overall decrease in the thickness of the cortex wall. In NPCs, Pml regulated the subcellular distribution of the retinoblastoma protein (pRb) and the protein phosphatase 1α, triggering pRb dephosphorylation. Together, these findings reveal an unexpected role of Pml in controlling the function of NPCs in the CNS.
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Acknowledgements
A special thank to P.P. Pandolfi (Beth Israel Deaconess Cancer Center) and R. Hevner (Seattle Children's Hospital Research Institute) for the Pml−/− mouse line and the antibody to Tbr2, respectively. We particularly thank D. Dinsdale, J. Edwards and R. Edwards (Medical Research Council Toxicology Unit) for support and assistance with immunohistochemistry. We also thank C. Watson (University of Cambridge), D. Read, G. Melino, R. Knight, and M. Capasso (Medical Research Council Toxicology Unit) for critical discussions. P.S., P.N., T.R. and C.B. are supported by the Medical Research Council. C.B. is a PhD, student at the University of Leicester.
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T.R. and P.S. designed and performed the experiments. C.B. performed a number of experments. P.N. provided expertise and contributed to experimental design and discussion. T.R. contributed to the writing of the manuscript. P.S. supervised the research project and wrote the manuscript.
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Regad, T., Bellodi, C., Nicotera, P. et al. The tumor suppressor Pml regulates cell fate in the developing neocortex. Nat Neurosci 12, 132–140 (2009). https://doi.org/10.1038/nn.2251
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DOI: https://doi.org/10.1038/nn.2251
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