Diffusion vs. direct transport in the precision of morphogen readout

TL;DR

This paper compares diffusion and direct transport mechanisms in morphogen profile formation, revealing that diffusion can be more precise than direct transport under certain conditions, supported by biological data.

Contribution

The study derives fundamental limits on morphogen sensing precision for diffusion and direct transport models, highlighting conditions where diffusion outperforms direct transport.

Findings

Diffusion can be more precise than direct transport for large populations and profile lengths.

Direct transport does not add extrinsic noise to morphogen profiles.

Biological data supports the theoretical predictions.

Abstract

Morphogen profiles allow cells to determine their position within a developing organism, but the mechanisms behind the formation of these profiles are still not well agreed upon. Here we derive fundamental limits to the precision of morphogen concentration sensing for two canonical models: the diffusion of morphogen through extracellular space and the direct transport of morphogen from source cell to target cell, e.g. via cytonemes. We find that direct transport establishes a morphogen profile without adding extrinsic noise. Despite this advantage, we find that for sufficiently large values of population size and profile length, the diffusion mechanism is many times more precise due to a higher refresh rate of morphogen molecules. Our predictions are supported by data from a wide variety of morphogens in developing organisms.