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

Vanderluit, Jacqueline L. and Wylie, Crystal A. and McClelland, Kelly A. and Ghanem, Noel and Fortin, Andre and Callaghan, Steve and MacLaurin, Jason G. and Park, David S. and Slack, Ruth S. (2007) The Retinoblastoma family member p107 regulates the rate of progenitor commitment to a neuronal fate. Journal of Cell Biology, 178 (1). pp. 129-139.

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Abstract

The Retinoblastoma protein p107 regulates the neural precursor pool in both the developing and adult brain. As p107-defi cient 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 defi ciency rescues neurosphere numbers in p107-null embryos. We fi nd 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-defi cient brains. Together, we identify a novel function for p107 in promoting neural progenitor commitment to a neuronal fate.

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