Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance

Elife. 2017 Jul 12:6:e24660. doi: 10.7554/eLife.24660.

Abstract

Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe (Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs. Further, Lfng in NSCs and Notch ligands Delta1 and Jagged1, expressed by their progeny, together influence NSC recruitment, cell cycle duration, and terminal fate. We propose a new model in which Lfng-mediated Notch signaling enables direct communication between a NSC and its descendants, so that progeny can send feedback signals to the 'mother' cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be a key factor governing NSC quiescence, division, and fate.

Keywords: Lineage tracing; Lunatic fringe; Notch signaling; adult hippocampal neurogenesis; developmental biology; mouse; mouse models; neural stem cells; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Proliferation
  • Gene Expression Regulation
  • Glycosyltransferases / metabolism*
  • Hippocampus / physiology*
  • Mice
  • Neural Stem Cells / physiology*
  • Receptors, Notch / metabolism*
  • Signal Transduction*

Substances

  • Receptors, Notch
  • Glycosyltransferases
  • Lfng protein, mouse