Rotation of sex combs in Drosophila melanogaster requires precise and coordinated spatio-temporal dynamics from forces generated by epithelial cells

The morphogenesis of sex combs (SCs), a male trait in many species of fruit flies, is an excellent system in which to study the cell biology, genetics and evolution of a trait. In Drosophila melanogaster, where the incipient SC rotates from horizontal to a vertical position, three signal comb properties have been documented: length, final angle and shape (linearity). During SC rotation, in which many cellular processes are occurring both spatially and temporally, it is difficult to distinguish which processes are crucial for which attributes of the comb. We have used a novel approach combining simulations and experiments to uncover the spatio-temporal dynamics underlying SC rotation. Our results indicate that 1) the final SC shape is primarily controlled by the inhomogeneity of initial cell size in cells close to the immature comb, 2) the final angle is primarily controlled by later cell expansion and 3) a temporal sequence of cell expansion mitigates the malformations generally associated with longer rotated SCs. Overall, our work has linked together the morphological diversity of SCs and the cellular dynamics behind such diversity, thus providing important insights on how evolution may affect SC development via the behaviours of surrounding epithelial cells.Author summary: The sex comb (SC) is a series of modified bristles on the male forelegs of many species of fruit flies. The size, position and shape of these sex combs vary drastically across different fly species. Therefore, SCs are a model system which illustrates the interaction between evolution and organism development influencing phenotypic features. In this work, we use a combined simulation-experimental approach to study the cellular processes involved in the rotation of developing SCs in common fruit flies (D. melanogaster). Our results indicate that despite the appearance of a complicated set of motions of surrounding cells associated with SC rotation, the final SC attributes only depend on a few selected parameters. We showed that changes in the timing and extent of cell size increase in distal cells altered the extent of SC rotation and breakage. Furthermore, these changes were sufficient to account for the observed variations in SC rotation between different fly species. Thus, our computational model has given us important insights on how evolution may use various cellular processes as a means to manifest the diversity of SCs across different fly species.