Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules

Nature. 2009 Sep 24;461(7263):533-6. doi: 10.1038/nature08391. Epub 2009 Sep 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diffusion
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism*
  • Endocytosis*
  • Extracellular Space / metabolism
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Gastrulation
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Models, Biological
  • Morphogenesis / physiology*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Zebrafish / embryology*
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Receptors, Fibroblast Growth Factor
  • Zebrafish Proteins
  • enhanced green fluorescent protein
  • fgf8a protein, zebrafish
  • Green Fluorescent Proteins
  • Fibroblast Growth Factors