Notch1 expression is spatiotemporally correlated with neurogenesis and negatively regulated by Notch1-independent Hes genes in the developing nervous system

Cereb Cortex. 2006 Jul:16 Suppl 1:i132-7. doi: 10.1093/cercor/bhj166.

Abstract

In the developing nervous system, neural stem cells initially proliferate by a symmetric cell division and then undergo an asymmetric cell division, which makes one neuron (or neuronal precursor) and one progenitor. It remains to be determined how the switch from the symmetric to asymmetric cell divisions is regulated. Here, we found that Notch1 is expressed in the regions where neurogenesis occurs actively but not in the regions where neurogenesis does not yet occur. Furthermore, in Hes-mutant mice where neurogenesis is accelerated, Notch1 expression is also accelerated. Thus, Notch1 expression is negatively regulated by Hes genes and is spatiotemporally correlated with neurogenesis, suggesting that the neural stem cells that undergo asymmetric cell divisions express Notch1, whereas those that undergo symmetric cell divisions do not. We propose that initiation of Notch1 expression is one of the key features for switch from the symmetric to asymmetric cell divisions of neural stem cells and that this process is negatively regulated by Notch1-independent Hes genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Division
  • Cells, Cultured
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / embryology*
  • Down-Regulation / physiology
  • Gene Expression Regulation, Developmental / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / physiology
  • Organogenesis / physiology
  • Receptor, Notch1 / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Statistics as Topic
  • Tissue Distribution
  • Transcription Factor HES-1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Hes3 protein, mouse
  • Hes5 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Repressor Proteins
  • Transcription Factor HES-1