Feedback regulation of cytoneme-mediated transport shapes a tissue-specific FGF morphogen gradient

Elife. 2018 Oct 17:7:e38137. doi: 10.7554/eLife.38137.


Gradients of signaling proteins are essential for inducing tissue morphogenesis. However, mechanisms of gradient formation remain controversial. Here we characterized the distribution of fluorescently-tagged signaling proteins, FGF and FGFR, expressed at physiological levels from the genomic knock-in alleles in Drosophila. FGF produced in the larval wing imaginal-disc moves to the air-sac-primordium (ASP) through FGFR-containing cytonemes that extend from the ASP to contact the wing-disc source. The number of FGF-receiving cytonemes extended by ASP cells decreases gradually with increasing distance from the source, generating a recipient-specific FGF gradient. Acting as a morphogen in the ASP, FGF activates concentration-dependent gene expression, inducing pointed-P1 at higher and cut at lower levels. The transcription-factors Pointed-P1 and Cut antagonize each other and differentially regulate formation of FGFR-containing cytonemes, creating regions with higher-to-lower numbers of FGF-receiving cytonemes. These results reveal a robust mechanism where morphogens self-generate precise tissue-specific gradient contours through feedback regulation of cytoneme-mediated dispersion.

Keywords: D. melanogaster; Drosophila; FGF; FGFR; branching morphogenesis; cytonemes; developmental biology; morphogen gradient.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Cell Surface Extensions
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Feedback, Physiological*
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation
  • Genome, Insect
  • Green Fluorescent Proteins / metabolism
  • Imaginal Discs / metabolism
  • Imaging, Three-Dimensional
  • Organ Specificity*
  • Protein Transport
  • Signal Transduction
  • Wings, Animal / metabolism


  • Drosophila Proteins
  • bnl protein, Drosophila
  • Green Fluorescent Proteins
  • Fibroblast Growth Factors