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Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal.

Nature | Sep 16, 2010

Specialized cellular microenvironments, or 'niches', modulate stem cell properties, including cell number, self-renewal and fate decisions. In the adult brain, niches that maintain a source of neural stem cells (NSCs) and neural progenitor cells (NPCs) are the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus. The size of the NSC population of the SVZ at any time is the result of several ongoing processes, including self-renewal, cell differentiation, and cell death. Maintaining the balance between NSCs and NPCs in the SVZ niche is critical to supply the brain with specific neural populations, both under normal conditions or after injury. A fundamental question relevant to both normal development and to cell-based repair strategies in the central nervous system is how the balance of different NSC and NPC populations is maintained in the niche. EGFR (epidermal growth factor receptor) and Notch signalling pathways have fundamental roles during development of multicellular organisms. In Drosophila and in Caenorhabditis elegans these pathways may have either cooperative or antagonistic functions. In the SVZ, Notch regulates NSC identity and self-renewal, whereas EGFR specifically affects NPC proliferation and migration. This suggests that interplay of these two pathways may maintain the balance between NSC and NPC numbers. Here we show that functional cell-cell interaction between NPCs and NSCs through EGFR and Notch signalling has a crucial role in maintaining the balance between these cell populations in the SVZ. Enhanced EGFR signalling in vivo results in the expansion of the NPC pool, and reduces NSC number and self-renewal. This occurs through a non-cell-autonomous mechanism involving EGFR-mediated regulation of Notch signalling. Our findings define a novel interaction between EGFR and Notch pathways in the adult SVZ, and thus provide a mechanism for NSC and NPC pool maintenance.

Pubmed ID: 20844536 RIS Download

Mesh terms: Animals | Cell Count | Cell Division | Humans | Membrane Proteins | Mice | Mice, Inbred C57BL | Nerve Tissue Proteins | Neurons | Protein Binding | Receptor, Epidermal Growth Factor | Receptor, Notch1 | Receptors, Notch | Signal Transduction | Stem Cell Niche | Stem Cells | Ubiquitination

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Associated grants

  • Agency: NINDS NIH HHS, Id: R01NS045702
  • Agency: NIDCD NIH HHS, Id: R01 DC006881-04
  • Agency: NIDCD NIH HHS, Id: R01DC006881
  • Agency: NICHD NIH HHS, Id: P30 HD040677
  • Agency: NINDS NIH HHS, Id: R01NS056427
  • Agency: NIDCD NIH HHS, Id: R01 DC006881
  • Agency: NINDS NIH HHS, Id: R01 NS045702
  • Agency: NICHD NIH HHS, Id: P30HD40677
  • Agency: NINDS NIH HHS, Id: K99 NS057944
  • Agency: NINDS NIH HHS, Id: K99NS057944
  • Agency: NINDS NIH HHS, Id: R00 NS057944
  • Agency: NIDCD NIH HHS, Id: R01 DC006881-03
  • Agency: NINDS NIH HHS, Id: R01 NS056427
  • Agency: NINDS NIH HHS, Id: R0O NS057944-03

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