A mechanism for the sharp transition of morphogen gradient interpretation in Xenopus

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Abstract
Background: One way in which positional information is established during embryonic development is through the graded distribution of diffusible morphogens. Unfortunately, little is known about how cells interpret different concentrations of morphogen to activate different genes or how thresholds are generated in a morphogen gradient. Results: Here we show that the concentration-dependent induction of the T-box transcription factor Brachyury (Xbra) and the homeobox-containing gene Goosecoid (Gsc) by activin in Xenopus can be explained by the dynamics of a simple network consisting of three elements with a mutual negative feedback motif that can function to convert a graded signal (activin) into a binary output (Xbra on and Gsc off, or vice versa). Importantly, such a system can display sharp thresholds. Consistent with the predictions of our model, Xenopus ectodermal cells display a binary response at the single cell level after treatment with activin. Conclusion: This kind of simple network with mutual negative feedback might provide a general mechanism for selective gene activation in response to different levels of a single external signal. It provides a mechanism by which a sharp boundary might be created between domains of different cell types in response to a morphogen gradient.