Response to the Dorsal Anterior Gradient of EGFR Signaling in Drosophila Oogenesis Is Prepatterned by Earlier Posterior EGFR Activation

•Localized early EGFR signaling thus regulates the response to later EGFR signaling•T-box proteins Mid and H15 are expressed in posterior follicle cells•Expression of Mid and H15 is induced by posterior EGFR signaling in early stages•Mid and H15 block EGFR-mediated dorsal anterior fate induction in posterior cells

SummarySpatially restricted epidermal growth factor receptor (EGFR) activity plays a central role in patterning the follicular epithelium of the Drosophila ovary. In midoogenesis, localized EGFR activation is achieved by the graded dorsal anterior localization of its ligand, Gurken. Graded EGFR activity determines multiple dorsal anterior fates along the dorsal-ventral axis but cannot explain the sharp posterior limit of this domain. Here, we show that posterior follicle cells express the T-box transcription factors Midline and H15, which render cells unable to adopt a dorsal anterior fate in response to EGFR activation. The posterior expression of Midline and H15 is itself induced in early oogenesis by posteriorly localized EGFR signaling, defining a feedback loop in which early induction of Mid and H15 confers a molecular memory that fundamentally alters the outcome of later EGFR signaling. Spatial regulation of the EGFR pathway thus occurs both through localization of the ligand and through localized regulation of the cellular response.

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