Opposing Feedbacks on Ras Tune Receptor Tyrosine Kinase Signaling

Signaling in development is not always on or off; often, distinct intensity and duration of signaling leads to distinct outcomes. This is true for receptor tyrosine kinase (RTK) signaling in many contexts, where negative feedback often plays a role. Although such negative feedback might reduce or even turn off signaling output over time, continued signaling is often maintained for proper cell fate specification. In this issue, Sieglitz et al. identify a positive regulator of Ras-mediated RTK signaling that they name Rau. Rau is necessary to achieve specific signaling intensity for the differentiation of photoreceptors and of glia that wrap axons in the developing Drosophila eye disc. Both the negative regulator Sprouty and Rau influence signaling through the guanosine triphosphatase Ras; specifically, Rau forms a positive feedback loop important for counteracting the Sprouty negative feedback loop.