Anatoly B. Kolomeisky, Rice University, Center for Theoretical Biological Physics

How to Understand the Formation of Signaling Profiles in Biological Development

Concentration profiles of signaling molecules, also known as morphogen gradients, play a critical role in the development of multi-cellular organisms. A widely used approach to explain the establishment of morphogen gradients assumes that signaling molecules are produced locally, spread via a free diffusion and degraded uniformly. However, recent experiments also produced controversial observations concerning this theoretical picture. It was shown that times to establish the morphogen gradient yield linear scaling as a function of length, not expected for the systems with unbiased diffusion. We propose a theoretical approach based on discrete-state stochastic analysis that provides a possible microscopic mechanism for these complex phenomena. It is argued that relaxation times are mostly determined by first-passage events, and the degradation effectively accelerates diffusion of signaling particles by removing slow molecules. Thus the degradation works as an effective potential that drives signaling molecules away from the source. Furthermore, we analyzed a direct-delivery mechanism of the formation of signaling profiles via cellular extensions known as cytonemes. Different mechanisms of the formation of morphogen gradients are compared. Our theoretical analysis indicates that spatial and temporal features of degradation efficiently control the establishment of signaling profiles.

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