Accuracy of positional information provided by multiple morphogen gradients with correlated noise.

Normal development of multicellular organisms requires cells to respond properly according to their positions. Positional information is often provided to cells as concentrations of diffusive chemicals called morphogens with spatial gradients. However, the spatial profiles of their concentrations include various kinds of noises, making positional information unreliable. In many developmental systems, multiple morphogen gradients are adopted to specify the spatial position along a single axis, presumably to achieve a sufficiently high precision of information on the location of each cell. In this paper, we ask how the precision of positional information depends on the number of morphogens. We derive a formula for the limit of precision when each cell adopts the maximum-likelihood estimation of the "true" position from noisy inputs. The precision increases with the number of morphogens and interestingly it also depends on the correlation of noises. The positional specification can be made more precisely if their gradients are of the opposite (same) direction when noises of the two morphogens are positively (negatively) correlated. The formula also tells us a minimum number of morphogens needed to achieve a given precision of positional information. We illustrate the theory by analyzing experimental data for the gradients of two diffusive chemicals, Bicoid and Caudal, in the early development of Drosophila embryo. The analysis suggests that combined information provided by the two chemicals is able to give accurate positional information in the middle part of the embryo, where the embryo segmentation occurs in later stages, much more than near both ends.