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GPI-anchored FGF directs cytoneme-mediated bidirectional signaling to self-regulate tissue-specific dispersion

Lijuan Du, Alex Sohr, Yujia Li, View ORCID ProfileSougata Roy
doi: https://doi.org/10.1101/2021.02.23.432493
Lijuan Du
1Department of Cell Biology and Molecular Genetics; University of Maryland, College Park, MD 20742, USA
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Alex Sohr
1Department of Cell Biology and Molecular Genetics; University of Maryland, College Park, MD 20742, USA
2Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
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Yujia Li
1Department of Cell Biology and Molecular Genetics; University of Maryland, College Park, MD 20742, USA
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Sougata Roy
1Department of Cell Biology and Molecular Genetics; University of Maryland, College Park, MD 20742, USA
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  • ORCID record for Sougata Roy
  • For correspondence: sougata@umd.edu
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ABSTRACT

How signaling proteins generate a multitude of information to organize tissue patterns is critical to understanding morphogenesis. In Drosophila, FGF produced in wing-disc cells regulates the development of the disc-associated air-sac-primordium (ASP). Here, we show that FGF is Glycosylphosphatidylinositol-anchored to the producing cell surface and that this modification both inhibits free FGF secretion and activates target-specific bidirectional FGF-FGFR signaling through cytonemes. FGF-source and recipient ASP cells extend cytonemes that present FGF and FGFR on their surfaces and reciprocally recognize each other over distance by contacting through CAM-like FGF-FGFR binding. Contact-mediated FGF-FGFR binding induces bidirectional signaling, which, in turn, promotes ASP and source cells to polarize cytonemes toward each other and reinforce signaling contacts. Subsequent un-anchoring of FGFR-bound-FGF from the source cell membrane dissociates cytoneme contacts and delivers FGF target-specifically to ASP cytonemes for paracrine functions. Thus, GPI-anchored FGF organizes both source and recipient cells and self-regulates its cytoneme-mediated tissue-specific dispersion and signaling.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • This revised manuscript was reviewed for publication and is the most recent version

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 05, 2022.
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GPI-anchored FGF directs cytoneme-mediated bidirectional signaling to self-regulate tissue-specific dispersion
Lijuan Du, Alex Sohr, Yujia Li, Sougata Roy
bioRxiv 2021.02.23.432493; doi: https://doi.org/10.1101/2021.02.23.432493
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GPI-anchored FGF directs cytoneme-mediated bidirectional signaling to self-regulate tissue-specific dispersion
Lijuan Du, Alex Sohr, Yujia Li, Sougata Roy
bioRxiv 2021.02.23.432493; doi: https://doi.org/10.1101/2021.02.23.432493

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