|Title||Feedback control of the EGFR signaling gradient: superposition of domain-splitting events in Drosophila oogenesis.|
|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Zartman, JJ, Kanodia, JS, Cheung, LS, Shvartsman, SY|
|Date Published||2009 Sep|
|Keywords||Animals, Body Patterning, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Enzyme Activation, Eye Proteins, Feedback, Physiological, Female, MAP Kinase Signaling System, Membrane Proteins, Mitogen-Activated Protein Kinases, Nerve Tissue Proteins, Oogenesis, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Receptor, Epidermal Growth Factor, Transcription Factors|
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.