Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis

Nat Commun. 2013:4:1880. doi: 10.1038/ncomms2895.

Abstract

Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Animals
  • Calcium-Binding Proteins
  • Cells, Cultured
  • Cerebral Ventricles / cytology
  • Gene Deletion
  • Green Fluorescent Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mitosis*
  • Models, Biological
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Receptors, Notch / metabolism

Substances

  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Notch
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins