Feedback control of the EGFR signaling gradient: superposition of domain-splitting events in Drosophila oogenesis. Author Jeremiah Zartman, Jitendra Kanodia, Lily Cheung, Stanislav Shvartsman Publication Year 2009 Type Journal Article Abstract The morphogenesis of structures with repeated functional units, such as body segments and appendages, depends on multi-domain patterns of cell signaling and gene expression. We demonstrate that during Drosophila oogenesis, the two-domain expression pattern of Broad, a transcription factor essential for the formation of the two respiratory eggshell appendages, is established by a single gradient of EGFR activation that induces both Broad and Pointed, which mediates repression of Broad. Two negative-feedback loops provided by the intracellular inhibitors of EGFR signaling, Kekkon-1 and Sprouty, control the number and position of Broad-expressing cells and in this way influence eggshell morphology. Later in oogenesis, the gradient of EGFR activation is split into two smaller domains in a process that depends on Argos, a secreted antagonist of EGFR signaling. In contrast to the previously proposed model of eggshell patterning, we show that the two-domain pattern of EGFR signaling is not essential for specifying the number of appendages. Thus, the processes that define the two-domain patterns of Broad and EGFR activation are distinct; their actions are separated in time and have different effects on eggshell morphology. Keywords Animals, Drosophila Proteins, Female, Drosophila melanogaster, Oogenesis, Membrane Proteins, Proto-Oncogene Proteins, Transcription Factors, Body Patterning, DNA-Binding Proteins, Receptor, Epidermal Growth Factor, Feedback, Physiological, Enzyme Activation, MAP Kinase Signaling System, Mitogen-Activated Protein Kinases, Protein Tyrosine Phosphatases, Eye Proteins, Nerve Tissue Proteins Journal Development Volume 136 Issue 17 Pages 2903-11 Date Published 09/2009 Alternate Journal Development Google ScholarBibTeXEndNote X3 XML