cis-Inhibition of Notch by endogenous Delta biases the outcome of lateral inhibition

Curr Biol. 2009 Aug 25;19(16):1378-83. doi: 10.1016/j.cub.2009.06.042. Epub 2009 Jul 23.


Lateral inhibition mediated by Delta/Notch (Dl/N) signaling is used throughout development to limit the number of initially equivalent cells that adopt a particular fate. Although adjacent cells express both Dl ligand and N receptor, signaling between them ultimately occurs in only one direction. Classically, this has been explained entirely by feedback: activated N can downregulate Dl, amplifying even slight asymmetries in the Dl or N activities of adjacent cells. Here, however, we present an example of lateral inhibition in which unidirectional signaling depends instead on Dl's ability to inhibit N within the same cell, a phenomenon known as cis-inhibition. By genetically manipulating individual R1/R6/R7 photoreceptor precursors in the Drosophila eye, we show that loss of Dl-mediated cis-inhibition reverses the direction of lateral signaling. Based on our finding that Dl in R1/R6s requires endocytosis to trans-activate but not to cis-inhibit N, we reexamine previously published data from other examples of lateral inhibition. We conclude that cis-inhibition generally influences the direction of Dl/N signaling and should therefore be included in standard models of lateral inhibition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Communication
  • Cell Lineage
  • Compound Eye, Arthropod / cytology
  • Compound Eye, Arthropod / growth & development*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Endocytosis
  • Epidermal Growth Factor / physiology
  • Feedback, Physiological
  • Intracellular Signaling Peptides and Proteins
  • Larva
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Models, Biological
  • Photoreceptor Cells, Invertebrate / cytology*
  • Photoreceptor Cells, Invertebrate / metabolism
  • Receptors, Notch / physiology*
  • Signal Transduction / physiology


  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • delta protein
  • Epidermal Growth Factor