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| The patterning of many developing tissues is orchestrated by gradients of morphogens through a variety of elaborate regulatory interactions. Such interactions are thought to make gradients robust--i.e. resistant to change in the face of genetic or environmental perturbations--but just how this might be done is a major unanswered question. Past numerical simulations and analytical studies suggest that robustness of signaling gradients cannot be attained by negative feedback (of the Hill's function type) on signaling receptors but can be achieved through morphogen degradation by non-signaling receptor molecules (or non-receptors for short) such as heparan sulfate proteoglycans. However, evidence of feedback regulating signaling gradients has been reported in the literature. The present paper undertakes a different approach to the role of feedback in robust signaling gradients. The overall goal of the project is to investigate the effective-ness of feedback on ligand synthesis, receptor-mediated degradation, non-receptor synthesis and other regulatory processes in morphogen gradient systems. As a first step, we present in this talk a proof of concept examination of a new spatially uniform feedback process that is distinctly different from the conventional spatially non-uniform Hill function approach.
(1)The research is supported in part by NIH Grants R01GM067247, and P50-GM076516. The R01 was awarded through the Joint NSF/ NIGMS Initiative to Support Research in the Area of Mathematical Biology.
(2) Undergraduate at St. Olaf College supported by the NSF REU awarded to MBI of Ohio State University to participate in the 2013 MCBU Program at U.C. Irvine.
(3) Department of Mathematics, University of California, Irvine |
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