Do morphogen gradients arise by diffusion?

Abstract

Many patterns of cell and tissue organization are specified during development by gradients of morphogens, substances that assign different cell fates at different concentrations. Gradients form by morphogen transport from a localized site, but whether this occurs by simple diffusion or by more elaborate mechanisms is unclear. We attempt to resolve this controversy by analyzing recent data in ways that appropriately capture the complexity of systems in which transport, receptor interaction, endo- and exocytosis, and degradation occur together. We find that diffusive mechanisms of morphogen transport are much more plausible-and nondiffusive mechanisms much less plausible-than has generally been argued. Moreover, we show that a class of experiments, endocytic blockade, thought to effectively distinguish between diffusive and nondiffusive transport models actually fails to draw useful distinctions.