TRANSIENT FEEDBACK AND ROBUST SIGNALING GRADIENTS.

Robust development of biological organisms in the presence of genetic and epi-genetic perturbations is important for time spans short relative to evolutionary time. Gradients of receptor bound signaling morphogens are responsible for patterning formation and development. A variety of inhibitors for reducing ectopic signaling activities are known to exist and their specific role in down-regulating the undesirable ectopic activities reasonably well understood. However, how a developing organism manages to adjust inhibition/stimulation in response to genetic and/or environmental changes remains to be uncovered. The need to adjust for ectopic signaling activities requires the presence of one or more feedback mechanisms to stimulate the needed adjustment. As the ultimate effect of many inhibitors (including those of the nonreceptor type) is to reduce the availability of signaling morphogens for binding with signaling receptors, a negative feedback on signaling morphogen synthesis rate based on a root-mean-square measure of the spatial distribution of signaling concentration offers a simple approach to robusness and has been demonstrated to be effective in a proof-of-concept implementation. In this paper, we complement the previous investigation of feedback in steady state by examining the effect of one or more feedback adjustments during the transient phase of the biological development.