title: Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.
abstract: It is widely accepted that tissue differentiation and morphogenesis in multicellular organisms are regulated by tightly controlled concentration gradients of morphogens. How exactly these gradients are formed, however, remains unclear. Here we show that Fgf8 morphogen gradients in living zebrafish embryos are established and maintained by two essential factors: fast, free diffusion of single molecules away from the source through extracellular space, and a sink function of the receiving cells, regulated by receptor-mediated endocytosis. Evidence is provided by directly examining single molecules of Fgf8 in living tissue by fluorescence correlation spectroscopy, quantifying their local mobility and concentration with high precision. By changing the degree of uptake of Fgf8 into its target cells, we are able to alter the shape of the Fgf8 gradient. Our results demonstrate that a freely diffusing morphogen can set up concentration gradients in a complex multicellular tissue by a simple source-sink mechanism.
authors.affiliation: Developmental Genetics, Biotechnology Center, TUD, Tatzberg 47-49, 01307 Dresden, Germany.
authors.forename: Shuizi Rachel
authors.initials: SR
authors.lastname: Yu
authors.forename: Markus
authors.initials: M
authors.lastname: Burkhardt
authors.forename: Matthias
authors.initials: M
authors.lastname: Nowak
authors.forename: Jonas
authors.initials: J
authors.lastname: Ries
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Petrásek
authors.forename: Steffen
authors.initials: S
authors.lastname: Scholpp
authors.forename: Petra
authors.initials: P
authors.lastname: Schwille
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
mesh_terms: D000818:Animals; D004058:Diffusion; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D004705:Endocytosis; D005110:Extracellular Space / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D054262:Gastrulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; C517774:fgf8a protein, zebrafish; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors