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

• Published in: eLife Vol. 7
• Main Authors: Du, Lijuan, Sohr, Alex, Yan, Ge, Roy, Sougata
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 17.10.2018; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Alleles; Analysis; Animals; Biochemistry; branching morphogenesis; Cell adhesion & migration; Cell Surface Extensions; Cloning; cytonemes; Developmental Biology; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Embryo; Feedback; Feedback, Physiological; FGF; FGFR; Fibroblast growth factor receptors; Fibroblast Growth Factors - metabolism; Fluorescence; Gene expression; Gene Expression Regulation; Genes; Genetic engineering; Genetically engineered foods; Genetically modified organisms; Genome, Insect; Green Fluorescent Proteins - metabolism; Growth factors; Imaginal Discs - metabolism; Imaging, Three-Dimensional; Independent sample; Insects; Microscopy; morphogen gradient; Morphogenesis; Organ Specificity; Physiological aspects; Protein Transport; Proteins; Scientists; Signal Transduction; Transcription factors; Wings, Animal - metabolism; United States > US; FGF; Drosophila; developmental biology; D. melanogaster; branching morphogenesis; cytonemes; FGFR; morphogen gradient
• ISSN: 2050-084X; 2050-084X
• 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 . 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 at higher and 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.