Cis-interactions between Notch and its ligands block ligand-independent Notch activity

Elife. 2014 Dec 8:3:e04415. doi: 10.7554/eLife.04415.


The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels, including receptor production, endocytosis, and degradation. Notch is further characterized by a twofold relationship with its Delta-Serrate (DSL) ligands, as ligands from opposing cells (trans-ligands) activate Notch, whereas ligands expressed in the same cell (cis-ligands) inhibit signaling. We show that cells without both cis- and trans-ligands can mediate Notch-dependent developmental events during Drosophila oogenesis, indicating ligand-independent Notch activity occurs when the receptor is free of cis- and trans-ligands. Furthermore, cis-ligands can reduce Notch activity in endogenous and genetically induced situations of elevated trans-ligand-independent Notch signaling. We conclude that cis-expressed ligands exert their repressive effect on Notch signaling in cases of trans-ligand-independent activation, and propose a new function of cis-inhibition which buffers cells against accidental Notch activity.

Keywords: D. melanogaster; Notch pathway; cell biology; developmental biology; oogenesis; signal transduction; stem cells.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Drosophila
  • Ligands
  • Oogenesis
  • Protein Binding
  • RNA Interference
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*


  • DNA Primers
  • Ligands
  • Receptors, Notch