  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.
