Department of Computational and Systems Biology, John Innes Centre, Norwich, UK.
Phys Biol. 2009 Nov 26;6(4):046020. doi: 10.1088/1478-3975/6/4/046020.
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 analyzing 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.
在发育过程中，尽管存在不可避免的波动，形态发生梯度仍能精确地确定基因表达边界的位置。最近的实验表明，一些形态发生梯度可能在达到稳定状态之前就被解读。理论工作预测，这种系统将对胚胎间波动更具鲁棒性。通过分析两个受实验启发的形态发生梯度形成模型，我们研究了在胚胎间波动、内部生化噪声和形态发生测量时间变化存在的情况下，由预稳定状态形态发生梯度决定的基因表达边界的位置精度。研究发现，在达到稳定状态之前，直接转录因子形态发生因子对内部噪声特别敏感，这对早期测量不利，即使在存在大的胚胎间波动的情况下也是如此。通过细胞膜受体解释的形态发生因子可以在达到稳定状态之前进行测量，而不会显著降低位置精度，前提是测量时间的波动较小。将我们的研究结果应用于实验，我们预测果蝇中的转录因子形态发生因子 Bicoid 不太可能在达到稳定状态之前被解释。我们还预测，爪蟾中的 Activin 和斑马鱼中的 Nodal，这些通过细胞膜受体解释的形态发生因子，可以在预稳定状态下被解码。
