Morphogens are molecules that are released at discrete locations in developing embryos and create spatially inhomogeneous patterns of cellular behavior (e.g. patterns of gene expression) at other locations. The mechanism usually invoked by biologists is one in which morphogen transport establishes a gradient in space, and cells at various locations adopt fates according to the concentration of morphogen they encounter. The minimal machinery required for this process is a means of morphogen production, a means of morphogen transport and, usually, a means of morphogen removal. Yet genetic data indicate that real morphogen gradient systems almost universally employ a variety of other complex mechanisms—such as feedback regulation of receptor synthesis, multiple classes of morphogen-binding molecules, co-receptors, secreted inhibitors, multiple morphogens, enzymes that modify co-receptors, enzymes that cleave inhibitors, and so forth. Such complexity is seen even in those gradient systems that appear to do little more than specify gene expression at one or two threshold levels, such as the decapentaplegic gradient in the fruit fly larval wing disc. These observations suggest that morphogen gradients perform more tasks than biologists traditionally recognize. We address this question by exploring the behaviors of mechanistic models of gradient formation and response in well-studied biological systems, with an emphasis on identifying how various types of complexity create strategies for achieving specific ends. Among the performance objectives that will be discussed are robustness of pattern to genetic and environmental perturbations, control over the timing of patterning, coordination between gradient systems, suppression of gene expression “noise”, and coordination of patterning with growth. Such analysis not only provides insight into the uses of morphogen gradient systems, but also illustrates the utility of model exploration for the reverse engineering of complex biological systems.
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