Diverse Paths to Morphogen Gradient Robustness

2 Summary The patterning of many developing tissues is orchestrated by gradients of morphogens. Included among the molecular events that drive the formation of morphogen gradients are a variety of elaborate regulatory interactions. It is widely thought that the purpose of such interactions is to make gradients robust—i.e. resistant to change in the face of genetic or environmental perturbations—but precisely how this might come about is a major unanswered question. Here we identify two highly effective robustness strategies that can be exploited by any morphogen gradient in which morphogen degradation can occur through uptake by cell surface molecules other than signaling receptors. One strategy exploits the effects of non-linearity, i.e. saturability, in the binding of morphogens to receptors; the other exploits feedback inhibition of receptor synthesis. Interestingly, in the decapentaplegic gradient of the Drosophila wing disc, just such feedback inhibition occurs, and cell surface, non-receptor, morphogen-binding molecules (proteoglycans) are known to be key regulators of gradient shape. Thus, the robustness strategies identified here may help explain some of the regulatory architecture of one of the best studied gradient systems.