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Internalization and end flux in morphogen gradient formation


Two simple reaction-diffusion systems of partial differential equations and auxiliary conditions governing the activities of diffusible ligands such as Dpp in anterior-posterior axis of Drosophila wing imaginal discs were previously formulated and investigated by numerical simulations in [Developmental Cell 2 (2002) 785-796]. System B focuses on diffusion, reversible binding with receptors and ligand-mediated degradation for a fixed receptor concentration uniform in time and space. System C extended this basic but meaningful model to allow for endocytosis, exocytosis and receptor synthesis and degradation. The present paper provides a mathematical underpinning for the computational studies of these two systems and some insight gained from our analysis. We will see for instance that the two boundary value problems governing the steady state for the two systems are identical in form. This result will enable us to avoid dealing with internalization explicitly when we investigate other complex morphogen activities such as the effects of (1) feedback and (2) diffusible and non-diffusible molecules competing for ligands and receptors to inhibit cell signaling and pattern formation. The principal contribution of the present work pertains to the extension of System C to allow for a ligand flux at the source end. The more general model has many significant consequences including the removal of a limitation of previous models on ligand synthesis rate for the existence of steady state behavior. Linear stability of the corresponding steady state behavior is established. While the actual decay rate of transients is less accessible in this new model, it is possible to obtain tight upper and lower bounds for the decay rate in terms of the (effective) degradation rate of the receptors and that of the ligand-receptor complexes. © 2005 Elsevier B.V. All rights reserved. All rights reserved.

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