Activated Notch2 signaling inhibits differentiation of cerebellar granule neuron precursors by maintaining proliferation

Neuron. 2001 Aug 30;31(4):557-68. doi: 10.1016/s0896-6273(01)00395-6.

Abstract

In the developing cerebellar cortex, granule neuron precursors (GNPs) proliferate and commence differentiation in a superficial zone, the external granule layer (EGL). The molecular basis of the transition from proliferating precursors to immature differentiating neurons remains unknown. Notch signaling is an evolutionarily conserved pathway regulating the differentiation of precursor cells of many lineages. Notch2 is specifically expressed in proliferating GNPs in the EGL. Treatment of GNPs with soluble Notch ligand Jagged1, or overexpression of activated Notch2 or its downstream target HES1, maintains precursor proliferation. The addition of GNP mitogens Jagged1 or Sonic Hedgehog (Shh) upregulates the expression of HES1, suggesting a role for HES1 in maintaining precursor proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cells, Cultured
  • Cerebellar Cortex / cytology*
  • Cerebellar Cortex / growth & development
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Green Fluorescent Proteins
  • Hedgehog Proteins
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Indicators and Reagents / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Luminescent Proteins / genetics
  • Membrane Proteins
  • Mice
  • Neurons / cytology*
  • Neurons / physiology
  • Proteins / genetics
  • Proteins / pharmacology
  • RNA, Messenger / analysis
  • Receptor, Notch2
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism*
  • Retroviridae / genetics
  • Serrate-Jagged Proteins
  • Signal Transduction / physiology*
  • Stem Cells / cytology*
  • Stem Cells / physiology
  • Trans-Activators / genetics
  • Transcription Factor HES-1
  • Transfection

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Hedgehog Proteins
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Indicators and Reagents
  • Intercellular Signaling Peptides and Proteins
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Luminescent Proteins
  • Membrane Proteins
  • Notch2 protein, mouse
  • Proteins
  • RNA, Messenger
  • Receptor, Notch2
  • Receptors, Cell Surface
  • Serrate-Jagged Proteins
  • Trans-Activators
  • Transcription Factor HES-1
  • Green Fluorescent Proteins