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

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Abstract

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.

Data availability

All data generated and analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1,2,3,4,5,6,7 and also for corresponding figure supplements wherever applicable. The source code for R plots in Figures 5 and 7 are provided.

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Author details

Lijuan Du

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

Competing interests
The authors declare that no competing interests exist.
Alex Sohr

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

Competing interests
The authors declare that no competing interests exist.
Ge Yan

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

Competing interests
The authors declare that no competing interests exist.
Sougata Roy

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States

For correspondence
sougata@umd.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2236-9277

Funding

National Institute of General Medical Sciences (R35GM124878)

Sougata Roy

National Heart, Lung, and Blood Institute (R00HL114867)

Sougata Roy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.