title: Visualizing long-range movement of the morphogen Xnr2 in the Xenopus embryo.
abstract: One way in which cells acquire positional information during embryonic development is by measuring the local concentration of a signaling factor, or morphogen, that is secreted by an organizing center . The ways in which morphogen gradients are established, particularly in vertebrates, remain obscure, although various suggestions have been made for the mechanisms by which signaling molecules traverse fields of cells. These include simple diffusion, "cytonemes", filopodia, "argosomes", and "transcytosis". In this study, we use a functional EGFP-tagged ligand to visualize long-range signaling in the Xenopus embryo in real time. Our results show that the TGF-beta family member Xnr2 is secreted efficiently from embryonic cells, and a new method of tissue recombination allows us to investigate the way in which the morphogen traverses multiple cell diameters. This reveals that Xnr2 exerts long-range effects by diffusing rapidly through the extracellular milieu of nonexpressing cells. No evidence has been obtained for long-range signaling through cytonemes, filopodia, argosomes, or transcytosis. In demonstrating that long-range signaling in the early Xenopus embryo occurs by diffusion rather than by these alternative routes, our results suggest that different morphogens in different developmental contexts use different means of transport.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
authors.forename: P Huw
authors.initials: PH
authors.lastname: Williams
authors.forename: Anja
authors.initials: A
authors.lastname: Hagemann
authors.forename: Marcos
authors.initials: M
authors.lastname: González-Gaitán
authors.forename: James C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D028341:Activins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers; D004058:Diffusion; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C118849:GDF3 protein, Xenopus; D036341:Intercellular Signaling Peptides and Proteins; C485173:STK38L protein, Xenopus; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C485184:enhanced green fluorescent protein; D028341:Activins; D049452:Green Fluorescent Proteins