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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. |
