Cell-cell interactions during neural development: Multiple types of lateral inhibitions involved in Drosophila eye development

Inhibitory signals of cellular differentiation from differentiating cells play an important role in regulating the number and spatial distribution of distinctive types of cells in developing tissues. Several types of inhibitory mechanisms of cellular differentiation have been identified by making full use of the developmental genetics of Drosophila compound eyes. These inhibitory mechanisms are distinct from each other in their signal transduction cascades and/or their role in the pattern formation of the developing Drosophila eye. The following events occur: firstly a diffusible protein, Scabrous (Sea), is required to confer regular spacings of the founder cells, R8 cells, or preommatidial clusters in the developing eye disc via an unknown signal transduction cascade, secondly the Notch-signalling is at least required for the single-out of the R8 cells within the pre-ommatidial cluster possibly by preventing other cells in the equivalent groups from adapting fates as R8 cells. Notch-signalling activates a simple signal cascade mediating communication between the plasma membrane and nucleus not via protein phosphorylation. In contrast, a novel diffusible ligand, Argos, was likely to be required subsequently to the selection of R8 cells. Argos was shown to inhibit the activation of a receptor tyrosine kinase, DER, and the subsequent signal transduction in the Ras/MAPK cascade (the third inhibitory mechanism). We proposed that the role of Argos is to regulate the number of differentiated cells by controlling cellular differentiation and subsequent programmed cell death. The distinct roles of these inhibitory signals in the developing Drosophila eye are discussed in detail.