GPI-anchored FGF directs cytoneme-mediated bidirectional contacts to regulate its tissue-specific dispersion

Lijuan Du, Alex Sohr, Yujia Li and Sougata Roy ()
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Lijuan Du: University of Maryland
Alex Sohr: University of Maryland
Yujia Li: University of Maryland
Sougata Roy: University of Maryland

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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 promotes target-specific cytoneme contacts and contact-dependent FGF release. FGF-source and ASP cells extend cytonemes that present FGF and FGFR on their surfaces and reciprocally recognize each other over distance by contacting through cell-adhesion-molecule (CAM)-like FGF-FGFR binding. Contact-mediated FGF-FGFR interactions induce bidirectional responses in ASP and source cells that, in turn, polarize FGF-sending and FGF-receiving cytonemes toward each other to reinforce signaling contacts. Subsequent un-anchoring of FGFR-bound-FGF from the source 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.

Date: 2022
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DOI: 10.1038/s41467-022-30417-1

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