PT  - JOURNAL ARTICLE
AU  - Lijuan Du
AU  - Alex Sohr
AU  - Yujia Li
AU  - Sougata Roy
TI  - GPI-anchored FGF directs cytoneme-mediated bidirectional signaling to self-regulate tissue-specific dispersion
AID  - 10.1101/2021.02.23.432493
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.02.23.432493
4099  - http://biorxiv.org/content/early/2022/04/05/2021.02.23.432493.short
4100  - http://biorxiv.org/content/early/2022/04/05/2021.02.23.432493.full
AB  - 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 StatementThe authors have declared no competing interest.