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Published online June 25, 2007
doi:10.1083/jcb.200703176
The Journal of Cell Biology, Vol. 178, No. 1, 129-139
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Vanderluit et al.
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Article

The Retinoblastoma family member p107 regulates the rate of progenitor commitment to a neuronal fate

Jacqueline L. Vanderluit, Crystal A. Wylie, Kelly A. McClellan, Noel Ghanem, Andre Fortin, Steve Callaghan, Jason G. MacLaurin, David S. Park, and Ruth S. Slack

Department of Cellular and Molecular Medicine, Ottawa Health Research Institute, Neuroscience Program, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada

Correspondence to Ruth S. Slack: rslack{at}uottawa.ca

The Retinoblastoma protein p107 regulates the neural precursor pool in both the developing and adult brain. As p107-deficient mice exhibit enhanced levels of Hes1, we questioned whether p107 regulates neural precursor self-renewal through the repression of Hes1. p107 represses transcription at the Hes1 promoter. Despite an expanded neural precursor population, p107-null mice exhibit a striking reduction in the number of cortical neurons. Hes1 deficiency rescues neurosphere numbers in p107-null embryos. We find that the loss of a single Hes1 allele in vivo restores the number of neural precursor cells at the ventricular zone. Neuronal birthdating analysis reveals a dramatic reduction in the rate of neurogenesis, demonstrating impairment in p107–/– progenitors to commit to a neuronal fate. The loss of a single Hes1 allele restores the number of newly generated neurons in p107-deficient brains. Together, we identify a novel function for p107 in promoting neural progenitor commitment to a neuronal fate.

J.L. Vanderluit's present address is Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada.

Abbreviations used in this paper: BS, binding site; CDKI, cyclin-dependent kinase inhibitor; IZ, intermediate zone; PCNA, proliferating cell nuclear antigen; PH3, phosphohistone H3; pRb, Rb protein; Rb, Retinoblastoma; SVZ, sub-VZ; VZ, ventricular zone.


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