title: Cellular interpretation of the long-range gradient of Four-jointed activity in the Drosophila wing.
abstract: To understand how long-range patterning gradients are interpreted at the cellular level, we investigate how a gradient of expression of the Four-jointed kinase specifies planar polarised distributions of the cadherins Fat and Dachsous in the Drosophila wing. We use computational modelling to test different scenarios for how Four-jointed might act and test the model predictions by employing fluorescence recovery after photobleaching as an in vivo assay to measure the influence of Four-jointed on Fat-Dachsous binding. We demonstrate that in vivo, Four-jointed acts both on Fat to promote its binding to Dachsous and on Dachsous to inhibit its binding to Fat, with a bias towards a stronger effect on Fat. Overall, we show that opposing gradients of Fat and Dachsous phosphorylation are sufficient to explain the observed pattern of Fat-Dachsous binding and planar polarisation across the wing, and thus demonstrate the mechanism by which a long-range gradient is interpreted.
authors.affiliation: Bateson Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Hale
authors.affiliation: Bateson Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Brittle
authors.affiliation: Bateson Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Fisher
authors.affiliation: School of Mathematics and Statistics, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Nicholas A M
authors.initials: NA
authors.lastname: Monk
authors.affiliation: Bateson Centre, University of Sheffield, Sheffield, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Strutt
mesh_terms: D000818:Animals; D019281:Dimerization; D004330:Drosophila / Q000033:anatomy & histology*; D029721:Drosophila Proteins / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D010766:Phosphorylation
chemical_list: D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; C095900:fj protein, Drosophila
keywords: D. melanogaster; Four-jointed; PCP; developmental biology; gradients; planar polarity; stem cells