Abstract
We characterized the establishment of an Epidermal Growth Factor Receptor (EGFR) organizing center (EOC) during leg development in Drosophila melanogaster. Initial EGFR activation occurs in the center of leg discs by expression of the EGFR ligand Vn and the EGFR ligand-processing protease Rho, each through single enhancers, vnE and rhoE, that integrate inputs from Wg, Dpp, Dll and Sp1. Deletion of vnE and rhoE eliminates vn and rho expression in the center of the leg imaginal discs, respectively. Animals with deletions of both vnE and rhoE (but not individually) show distal but not medial leg truncations, suggesting that the distal source of EGFR ligands acts at short-range to only specify distal-most fates, and that multiple additional ‘ring’ enhancers are responsible for medial fates. Further, based on the cis-regulatory logic of vnE and rhoE we identified many additional leg enhancers, suggesting that this logic is broadly used by many genes during Drosophila limb development.
| Original language | English (US) |
|---|---|
| Article number | e1007568 |
| Journal | PLoS genetics |
| Volume | 14 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2018 |
Bibliographical note
Funding Information:This work was funded by National Institutes of Health grants R35GM118336 and RO1GM058575 awarded to RSM; by the National Institutes of Health training grant 5T32DK007328 awarded to SN; and by Leukemia and Lymphoma Society grant 5250-12 awarded to RV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to Drs. Myriam Zecca, Yannis Mavromatakis, Gerard Campbell, Gary Struhl, Amanda Simcox, Benny Shilo, Andrew Tomlinson, Carlos Estella, Jessica Treisman, Josepha Steinhauer, Gerardo Jimenez, Rebecca Spokony and Trudi Schupbach for sharing numerous reagents that greatly facilitated this study. We thank members of the Mann lab, Gary Struhl, and Harmen Bussemaker for comments and suggestions during the course of these studies.
Publisher Copyright:
© 2018 Newcomb et al. http://creativecommons.org/licenses/by/4.0/.