cis-regulatory architecture of a short-range EGFR organizing center in the Drosophila melanogaster leg

• Published in: PLoS genetics 2018-08, Vol.14 (8), p.e1007568-e1007568
• Main Authors: Newcomb, Susan, Voutev, Roumen, Jory, Aurelie, Delker, Rebecca K, Slattery, Matthew, Mann, Richard S
• Format: Article
• Language: English
• Subjects: Alleles; Animal development; Animals; Biochemistry; Biology; Biology and Life Sciences; Biophysics; CRISPR; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Drosophila Proteins - physiology; Enhancer Elements, Genetic; Enhancers; Epidermal growth factor; Epidermal growth factor receptors; Epidermal growth factors; ErbB Receptors - genetics; ErbB Receptors - physiology; Extremities - growth & development; Funding; Gene Deletion; Gene expression; Gene Expression Regulation, Developmental; Genetic aspects; Genomes; Genotype & phenotype; Health aspects; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Imaginal discs; Imaginal Discs - physiology; Insects; Leg; Ligands; Medicine and Health Sciences; Neuregulins - genetics; Neuregulins - physiology; Organizers, Embryonic; Physiological aspects; Receptors, Invertebrate Peptide - genetics; Receptors, Invertebrate Peptide - physiology; Research and Analysis Methods; Signal Transduction; Sp1 protein; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - physiology; Transcription Factors - genetics; Transcription Factors - physiology; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - physiology; Wnt1 Protein - genetics; Wnt1 Protein - physiology
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1007568

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.