PgmNr D1469: Expression of reciprocal antagonists Mirr and Mid is regulated by localized input from EGFR, JAK/STAT, and Dpp signaling pathways.

Authors:
Scott De Vito 1 ; Mariana Fregoso Lomas 1 ; Jean François Boisclair Lachance 2 ; Josée Houde 1 ; Laura Nilson 1


Institutes
1) Department of Biology, McGill University, Montreal, Quebec, CA; 2) Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois, USA.


Keyword: pattern formation

Abstract:

EGFR signalling is central to tissue patterning. In Drosophila ovarian follicular epithelium, EGFR signalling is activated by Grk, a ligand secreted by the oocyte.  Localized secretion of Grk leads  to localized EGFR signalling, which in turn specifies distinct cell fates at different stages . In early oogenesis, Grk/EGFR signalling at the posterior induces a posterior fate characterized by expression of the paralogous T-box transcription factors Mid and H15. In later stages, dorsal anterior Grk/EGFR signalling induces dorsal anterior fates characterized by the expression of the transcription factor Mirr.  These fates contribute to structure of the eggshell. Patterning of this epithelium thus involves activation of the same signalling pathway leading to different outcomes in different regions of the tissue. Here we show that EGFR signalling outcome is determined by spatially localized input from other signalling pathways. Here we show that at the anterior of the epithelium, Dpp signalling cooperates with Grk to induce expression of Mirr while also repressing Mid and H15. At the posterior of the epithelium, JAK/STAT signalling is required for expression of Mid and H15 while also repressing Mirr. Moreover, we show that Mid and Mirr mutually repress each other, contributing to the complementary expression of Mirr in the dorsal anterior and Mid at the posterior. Input from Dpp and JAK/STAT signalling thus defines whether  EGFR activity will induce expression of Mirr or expression of Mid/H15, and this choice is refined by the  mutual repression between Mirr and Mid/H15. The components comprise a molecular switch where graded inputs are converted into bistable outcomes.



Flybase Genetic Index:
1. FlyBase gene symbol: mid; FBgn: FBgn0261963
2. FlyBase gene symbol: mirr; FBgn: FBgn0014343
3. FlyBase gene symbol: tkv; FBgn: FBgn0003716
4. FlyBase gene symbol: Stat92e; FBgn: FBgn0016917
5. FlyBase gene symbol: hop; FBgn: FBgn0004864
6. FlyBase gene symbol: dome; FBgn: FBgn0043903
7. FlyBase gene symbol: mad; FBgn: FBgn0011648
8. FlyBase gene symbol: upd1; FBgn: FBgn0004956
9. FlyBase gene symbol: br; FBgn: FBgn0283451
10. FlyBase gene symbol: H15; FBgn: FBgn0016660