Spatial control of BMP pathway by EGFR signaling in Drosophila oogenesis

Nir Yakoby1, Jessica Lembong1, Christopher A. Bristow1, Trudi Schupbach2, Stanislav Y. Shvartsman1. 1) Dept of Genomics and Chemichal Engineering,Princeton University, Princeton, NJ; 2) HHMI, Dept of Molecular Biology, Princeton University, Princeton, NJ.

The BMP and EGFR pathways interact in a large number of developmental contexts, but the mechanisms of signal integration are only beginning to be explored. Signal integration can occur at the level of common transcriptional targets, and at the level of signal transduction. We show that during Drosophila egg development, the EGFR pathway can potentiate BMP signaling at the level of signal reception, by regulating the expression of multiple BMP receptors. In oogenesis, the EGFR and BMP pathways pattern the follicular epithelium by the emanating oocyte-derived Gurken ligand and Dpp secreted from the stretch cells. The first stage of BMP signaling is uniform along the DV axis has only the AP polarity, and mediated by Tkv and Put receptors uniformly expressed in the follicular epithelium. We discovered that later in oogenesis BMP signaling acquires a clear DV polarity. At this stage of signaling the BMP receptors Tkv, Put and Wit are expressed in dorsal-anterior patterns, which overlap the expression of known dorsal-anterior genes, such as Br and Rho. We demonstrate that these patterns are directly controlled by the EGFR pathway, and show that they are translated into the DV pattern of the BMP signaling at the level of pMad nuclear localization. These observations lead to a model where EGFR signaling provides the spatial control of BMP pathway by regulating the expression of its receptors. This model predicts the existence of targets that exhibit coordinate responses to variations in the levels of signaling through both pathways. We demonstrate that this is indeed the case for Br, a gene that marks the roof of the future dorsal appendages. We provide further support for this model by presenting the analysis of our genome-wide transcriptional profiling of EGFR and BMP signaling in the follicular epithelium. We argue that this type of pathway transactivation provides a novel strategy for the spatiotemporal coordination of signals in development.

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