Diffusion vs. direct transport in the precision of morphogen readout

Morphogen profiles allow cells to determine their position within a developing organism, but not all morphogen profiles form by the same mechanism. Here, we derive fundamental limits to the precision of morphogen concentration sensing for two canonical mechanisms: the diffusion of morphogen through extracellular space and the direct transport of morphogen from source cell to target cell, for example, via cytonemes. We find that direct transport establishes a morphogen profile without adding noise in the process. Despite this advantage, we find that for sufficiently large values of profile length, the diffusion mechanism is many times more precise due to a higher refresh rate of morphogen molecules. We predict a profile lengthscale below which direct transport is more precise, and above which diffusion is more precise. This prediction is supported by data from a wide variety of morphogens in developing Drosophila and zebrafish.