Diffusion of messages and messengers and the formation of morphogen gradients

PONCE DAWSON, SILVINA

Conferencia; Montevideo Dynamical Systems Conference 2012,; 2012

Diffusion is key to many physiologically relevant processes. It is particularly relevant for the formation of morphogen gradients which induce the differentiation of otherwise undifferentiated cells. One of the most widely studied morphogens is Bicoid (Bcd) which distribu- tion is determinant for the organization of the anterior-posterior axis in Drosophila embryos [1]. About 80 minutes after egg deposition a stable Bcd gradient is established with larger Bcd concentrations at the an- terior pole and an exponential decay towards the posterior end. This exponential distribution is consistent with the so called SDD model in which the protein is synthesized at the anterior end and subsequently diffuses and is degraded throughout the embryo. Within this model the Bcd diffusion coefficient is key to set the timescale over which the Bcd gradient forms and becomes stable. The Bcd diffusion coefficient was estimated using two optical techniques: Fluorescence Recovery After Photobleaching (FRAP) [2] and Fluorescence Correlation Spectroscopy (FCS) [3]. FRAP gave values that were too small to account for the es- tablishment of the gradient within SDD model and the experimentally observed times. FCS gave several values one of which was compatible with the SDD model. The questions then arise of what is the correct estimate and whether the SDD model can still explain the gradient formation or not. In this talk I will show the results of a collabo- rative work with Lorena Sigaut, Alejandro Colman-Lerner and John E. Pearson in which we use a simple biophysical model to deal with this issue [4]. In particular, I will show that both the FRAP and the FCS estimates are correct and that their difference is perfectly under- standable in terms of reactions of Bcd with binding sites [5]. It is the nonlinearities intrinsic to the reactions that are ultimately responsible for the disparity of the estimates one of which describes the diffusion of individual Bcd molecules (the messengers) and the other one that of their population (the message) [6].