When it Pays to Rush: Interpreting Morphogen Gradients Prior to Steady-State

TL;DR

This study investigates how morphogen gradients can be interpreted before reaching steady-state during development, analyzing the effects of fluctuations and noise on positional accuracy, and predicting which morphogens are suitable for early interpretation.

Contribution

The paper provides a comparative analysis of pre-steady-state morphogen interpretation, highlighting the conditions under which early measurement is feasible and identifying specific morphogens suitable for it.

Findings

Direct transcription factor morphogens are sensitive to internal noise when interpreted early.

Receptor-mediated morphogens can be measured pre-steady-state with minimal loss of precision.

Bicoid is unlikely to be interpreted pre-steady-state, while Activin and Nodal can be.

Abstract

During development, morphogen gradients precisely determine the position of gene expression boundaries despite the inevitable presence of fluctuations. Recent experiments suggest that some morphogen gradients may be interpreted prior to reaching steady-state. Theoretical work has predicted that such systems will be more robust to embryo-to-embryo fluctuations. By analysing two experimentally motivated models of morphogen gradient formation, we investigate the positional precision of gene expression boundaries determined by pre-steady-state morphogen gradients in the presence of embryo-to-embryo fluctuations, internal biochemical noise and variations in the timing of morphogen measurement. Morphogens that are direct transcription factors are found to be particularly sensitive to internal noise when interpreted prior to steady-state, disadvantaging early measurement, even in the presence of large embryo-to-embryo fluctuations. Morphogens interpreted by cell-surface receptors can be measured prior to steady-state without significant decrease in positional precision provided fluctuations in the timing of measurement are small. Applying our results to experiment, we predict that Bicoid, a transcription factor morphogen in Drosophila, is unlikely to be interpreted prior to reaching steady-state. We also predict that Activin in Xenopus and Nodal in zebrafish, morphogens interpreted by cell-surface receptors, can be decoded in pre-steady-state.