In an adult retina mutant for the spalt complex (right), all PRCs express the outer-PRC-specific rhodopsin gene. Left, wild-type. Photo provided by Bertrand Mollereau, The Rockefeller University, New York, USA. Reproduced with permission from Mollereau, B. et al. Nature © (2001) Macmillan Magazines Ltd.

The regular tiling of the Drosophila adult eye — a precise array of ∼800 units, or ommatidia — is a familiar sight to developmental biologists, who have used this organ to investigate how neuronal determination and differentiation occurs. Anatomical studies, and more recently, molecular genetic ones, have established that the eight photoreceptor cells (PRC 1–8) in each ommatidium arise through a series of stereotypical inductive interactions that take place in the larva. What isn't clear, however, is when each PRC makes the irreversible commitment to a specific fate. It is commonly thought that such a commitment is made in the larva, when each PRC expresses a distinct set of molecular markers; but Mollereau, Domínguez and colleagues now show that PRC determination occurs in two steps, each under separate genetic control. They do so by identifying the spalt (sal) gene complex as one component of this control.

The eight types of PRC are recognizable not only by their molecular markers, but also by their distinct position within the ommatidium, their morphology and by the types of projection that they make to the optic lobe. PRCs 1–6 — the outer photoreceptors — have larger light-trapping organelles (rhabdomeres) and make axonal projections to the lamina; by contrast, the smaller, inner PRCs 7 and 8 project deeper in the optic lobe, to the medulla. The zinc-finger proteins encoded by the two genes of the sal gene complex, sal major (salm) and sal-related (salr), have similar expression patterns and functions in eye development. When the sal complex is removed from the eye (using a chromosomal deficiency), PRCs 7 and 8 of each ommatidium are cell-autonomously transformed into outer photoreceptors. However, the axons of the transformed PRC 7 and 8 cells project normally to the medulla, indicating that sal is not required for the initial inner PRC specification. Such a function for the sal-encoded proteins is consistent with their expression pattern: although salm is expressed in PRCs 3 and 4 in the larva, it is only present in PRCs 7 and 8 in the pupa and adult, at a time that coincides with R7 and 8 differentiation.

The data lead nicely to a model in which PRC development occurs in two steps: first, cells differentiate as neurons and send axonal projections to the brain; it's only in the second that they become mature PRCs and execute their differentiation programme. In such a model, the sal complex would be required for the terminal differentiation of PRCs 7 and 8, but not for the initial acquisition of neural characteristics by these cells.