Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition

Dev Cell. 2010 Jul 20;19(1):78-89. doi: 10.1016/j.devcel.2010.06.006.

Abstract

The organization of bristles on the Drosophila notum has long served as a popular model of robust tissue patterning. During this process, membrane-tethered Delta activates intracellular Notch signaling in neighboring epithelial cells, which inhibits Delta expression. This induces lateral inhibition, yielding a pattern in which each Delta-expressing mechanosensory organ precursor cell in the epithelium is surrounded on all sides by cells with active Notch signaling. Here, we show that conventional models of Delta-Notch signaling cannot account for bristle spacing or the gradual refinement of this pattern. Instead, the pattern refinement we observe using live imaging is dependent upon dynamic, basal actin-based filopodia and can be quantitatively reproduced by simulations of lateral inhibition incorporating Delta-Notch signaling by transient filopodial contacts between nonneighboring cells. Significantly, the intermittent signaling induced by these filopodial dynamics generates a type of structured noise that is uniquely suited to the generation of well-ordered, tissue-wide epithelial patterns.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning / physiology*
  • Drosophila / genetics
  • Drosophila / growth & development*
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Gene Expression Regulation, Developmental
  • Genes, Insect
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Models, Biological
  • Pseudopodia / genetics
  • Pseudopodia / physiology*
  • Receptors, Notch / genetics
  • Receptors, Notch / physiology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • Recombinant Proteins
  • delta protein
  • Green Fluorescent Proteins