title: Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition.
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.
authors.affiliation: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, London, WC1E 6BT, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen
authors.forename: Marios
authors.initials: M
authors.lastname: Georgiou
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Stevenson
authors.forename: Mark
authors.initials: M
authors.lastname: Miodownik
authors.forename: Buzz
authors.initials: B
authors.lastname: Baum
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D011554:Pseudopodia / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D011994:Recombinant Proteins; C064045:delta protein; D049452:Green Fluorescent Proteins