Multiple feedback loops achieve robust localization of wingless expression in Drosophila notum development

Organ morphogenesis starts with the spatial patterning of different gene expressions in organ primordia, which is based on positional information provided by morphogens. To generate precise positional information, the robust localization of morphogen sources is needed. This can be realized by several different mechanisms, such as (i) by reducing the variations in spatial arrangement of morphogen sources, (ii) by reducing the variations in their source levels, and (iii) by increasing the degree of source localization with the sharp boundary that makes morphogen gradients steeper. Here we focus on the mechanism of localization of wingless expression, one of the important morphogens in Drosophila notum development. The mechanism of wingless-localization can be explained by a simple feed-forward loop network motif, but the real molecular network adopted by the organism is much more complex; it includes multiple feedback loops that function with the feed-forward loop in a coordinated manner. To clarify the functions of the molecular network, we decompose it into three sub-modules, each of which includes a single feedback loop, and examine their possible roles using a mathematical model. We demonstrate how the regulatory network for wingless expression realizes the conditions (i)-(iii) for its robust localization.

► We model the regulatory network of wg expression in Drosophila notum development. ► It is decomposed into three modules each of which includes a single feedback loop. ► Modular analyses reveal how each module contributes to robust localization of wg. ► Possible ways of verification of predicted modules' functions are discussed.