Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells

Nat Neurosci. 2015 May;18(5):657-65. doi: 10.1038/nn.3989. Epub 2015 Mar 30.

Abstract

The mechanism by which adult neural stem cells (NSCs) are established during development is unclear. In this study, analysis of cell cycle progression by examining retention of a histone 2B (H2B)-GFP fusion protein revealed that, in a subset of mouse embryonic neural progenitor cells (NPCs), the cell cycle slows between embryonic day (E) 13.5 and E15.5 while other embryonic NPCs continue to divide rapidly. By allowing H2B-GFP expressed at E9.5 to become diluted in dividing cells until the young adult stage, we determined that a majority of NSCs in the young adult subependymal zone (SEZ) originated from these slowly dividing embryonic NPCs. The cyclin-dependent kinase inhibitor p57 is highly expressed in this embryonic subpopulation, and the deletion of p57 impairs the emergence of adult NSCs. Our results suggest that a substantial fraction of adult SEZ NSCs is derived from a slowly dividing subpopulation of embryonic NPCs and identify p57 as a key factor in generating this embryonic origin of adult SEZ NSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Division
  • Cell Lineage
  • Cyclin-Dependent Kinase Inhibitor p57 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics
  • Cyclin-Dependent Kinase Inhibitor p57 / physiology*
  • Genes, Reporter
  • Histones / biosynthesis
  • Histones / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neural Stem Cells / cytology*
  • Neurogenesis*
  • Recombinant Fusion Proteins / metabolism
  • Telencephalon / cytology*
  • Telencephalon / embryology

Substances

  • Cyclin-Dependent Kinase Inhibitor p57
  • Histones
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins