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

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.

• Publication year

  2007

• Venue

  Journal of Cell Biology

• Publication date

  2007-07-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200703176PMID 17591923PMCID 2064429
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2006influential reference
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  2005influential reference
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  2005cited by this paper
• Roles of bHLH genes in neural stem cell differentiation.

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  2004influential reference
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  2003influential reference
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  2002cited by this paper
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  2002influential reference
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  2002cited by this paper
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  2001cited by this paper
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  2001influential reference
• Hematopoietic stem cell quiescence maintained by p21cip1/waf1.

  2000cited by this paper
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• In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain.

  1998cited by this paper
• The retinoblastoma gene family is differentially expressed during embryogenesis

  1997cited by this paper
• Mammalian hairy and Enhancer of split homolog 1 regulates differentiation of retinal neurons and is essential for eye morphogenesis.

  1996cited by this paper
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  1995influential reference
• Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model

  1995cited by this paper
• Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements.

  1994cited by this paper
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  1994cited by this paper
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  1992cited by this paper
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  1992influential reference
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  1989cited by this paper
• Development of neocortical afferent systems: studies in the reeler mouse.

  1982cited by this paper

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  2017cites this paper
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  2016cites this paper
• Tissue-specific targeting of cell fate regulatory genes by E2f factors

  2015cites this paper
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