Architects of any structure know the importance of defining the limits and orientation of a building. The top and bottom must be established and maintained, with interactions between all walls, ceilings and floors closely regulated. Cellular architecture is similarly regulated, with the ceiling (apical), floor (basal) and walls (basolateral) being defined and maintained. Nowhere is this architecture more clearly visualized than in the epithelial cells of Drosophila melanogaster. Although many genes that regulate the architecture of these cells have been identified, only now does new work in Nature Cell Biology indicate how these individual players might come together as one construction team.

Polarized Drosophila epithelial cells contain numerous membrane domains with distinct proteins involved in their maintenance. The bazooka group, the crumbs group and the discs-large/scribble group all have precise roles in apical–basal membrane polarity. Formation of a functional zonula adherens (a belt-like adhesion junction which encircles the whole cell) is of primary importance to most epithelial cells, with mutations in all three groups of genes mentioned above affecting this process. By analysing genetic relationships between these three groups, Bilder et al. and Tanentzapf & Tepass indicate that these three groups of genes could act co-operatively to order the formation of polarity in an integrated hierarchy.

Genetic analysis in Drosophila is a powerful tool in understanding how different protein complexes regulate the function of one another. By determining the epistatic relationship of one gene to another, the functional interactions of different protein complexes can be ascertained. By applying this analysis to study the development of apical–basolateral polarity, Bilder et al and Tanentzapf & Tepass tentatively ordered the three groups of genes into a construction network. It seems that the bazooka group is the top of the genetic hierarchy and acts to initiate zonula adherens assembly and establish apical polarity. The activity of the Bazooka group is counteracted by the Discs-large group, which is recruited independently to the basolateral membrane and represses the ability of the Bazooka group to induce apical membrane formation, and recruitment of the Crumbs group, in this region. Although the Discs-large group also appears to counteract the activity of the apical-inducing Crumbs group, Bilder et al suggest that the Crumbs group could also act to antagonize the activity of the Discs-large group, creating a complex network of interactions.

Whether these groups of proteins physically interact with one another to generate this network, which regulates polarity and determines zonula adherens formation, is unknown. Yet these three groups resemble the very best in construction expertise as they sensitively balance activity with one another to ensure correct establishment of polarity and cellular architecture.