title: Free extracellular diffusion creates the Dpp morphogen gradient of the Drosophila wing disc.
abstract: BACKGROUND
  How morphogen gradients form has long been a subject of controversy. The strongest support for the view that morphogens do not simply spread by free diffusion has come from a variety of studies of the Decapentaplegic (Dpp) gradient of the Drosophila larval wing disc.
  
  
  RESULTS
  In the present study, we initially show how the failure, in such studies, to consider the coupling of transport to receptor-mediated uptake and degradation has led to estimates of transport rates that are orders of magnitude too low, lending unwarranted support to a variety of hypothetical mechanisms, such as "planar transcytosis" and "restricted extracellular diffusion." Using several independent dynamic methods, we obtain data that are inconsistent with such models and show directly that Dpp transport occurs by simple, rapid diffusion in the extracellular space. We discuss the implications of these findings for other morphogen systems in which complex transport mechanisms have been proposed.
  
  
  CONCLUSIONS
  We believe that these findings resolve a major, longstanding question about morphogen gradient formation and provide a solid framework for interpreting experimental observations of morphogen gradient dynamics.
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhou
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Lo
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Suhalim
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Digman
authors.forename: Enrico
authors.initials: E
authors.lastname: Gratton
authors.forename: Qing
authors.initials: Q
authors.lastname: Nie
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Lander
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D005110:Extracellular Space / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D007814:Larva; D021381:Protein Transport; D013050:Spectrometry, Fluorescence / Q000379:methods; D014921:Wings, Animal / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C064196:dpp protein, Drosophila