Messages Do Diffuse Faster than Messengers: Reconciling Disparate Estimates of the Morphogen Bicoid Diffusion Coefficient

Lorena Sigaut, John E. Pearson, Alejandro Colman-Lerner, Silvina Ponce Dawson

Abstract: Author Summary Understanding the mechanisms by which equivalent cells develop into different body parts is a fundamental question in biology. One well-studied example is the patterning along the anterior-posterior axis of Drosophila melanogaster embryos for which the spatial gradient of the protein Bicoid is determinant. The localized production of Bicoid is implicated in its inhomogeneous distribution. Diffusion then determines the time and spatial scales of the gradient as it is formed. Estimates of Bicoid diffusion coefficients made with the optical techniques, FRAP and FCS resulted in largely different values, one of which was too slow to account for the observed time of gradient formation. In this paper, we present a model in which Bicoid diffuses and interacts with binding sites so that its transport is described by a "single molecule'' and a "collective'' diffusion coefficient. The latter can be arbitrarily larger than the former coefficient and sets the rate for bulk processes such as the formation of the gradient. In this way we obtain a self-consistent picture in which the FRAP and FCS estimates are accurate and where the gradient can be established within the experimentally observed times.