Structure of the Drosophila compound eye
Drosophila melanogaster has large compound eyes each containing about 800 similar facets (or ommatidia, see Figure 1, 1, 2, 3). Each ommatidium is comprised of twenty cells falling into twelve cell types: eight photoreceptor cells of three types (the outer cells: R1 - R6, the apical central R7 and the basal central R8), and twelve accessory cells of six types (see Figure 2, 1, 2-4). All of these cells are conventionally assigned to the retina. Visual acuity depends upon cell geometry and number (5, 6) and thus compound eye development must be particularly precise: so much so that the fly eye has been called a "neurocrystalline lattice"(3, 7). The morphological processes that underlie the development of the fly retina have been described in exquisite detail at the light and EM levels, such that it is possible to follow the specification and differentiation of each cell type as it occurs: we know the entire process from the last mitosis to the elaboration of adult morphology for each cell (3, 8-12). In addition there are antigenic and beta-galactosidase reporters available to mark all of the retinal cell types almost from their specification (13-21). This permits the detailed understanding of developmental mutants at a level far beyond that available in other systems. As the eye is a dispensable organ, mutations specific to eye development can be recovered as homozygotes, and this adds greatly to the facility (and thus power) of genetic screens (22-28). This level of sophistication in developmental analysis, coupled with the power of Drosophila genetic and molecular techniques have made the fly eye the preeminent invertebrate model for visual system development.

figure 1	figure 2

Eye development part I: the main events

Early in life about twenty cells are set aside to form the future eye and these form a columnar epithelium in the eye-antennal imaginal disc (29). The eye field is specified through the interaction of a number of genes including eyeless, eyes absent, eye gone, dachshund and sine oculis (30-37). Throughout early larval life this epithelium grows by unpatterned proliferation and in late larval life an invagination is formed on the apical surface of the eye field at its posterior margin (3, 7, 9, 12, 38-43). This "transverse groove" or "morphogenetic furrow" moves across the eye epithelium as a vertical line, from posterior to anterior over a period of about two days (see Figure 3, 3, 44). As it does so it lays down successive columns of ommatidial preclusters, approximately one every two hours (45). In the furrow cells apical profiles become small (as they are drawn in by contractile rings of cytoplasmic actin) and all cells are held in G1 arrest (9, 11, 46, 47).

figure 3

In the furrow the first evident ommatidial stage are cores of about four cells surrounded by rings of fifteen to seventeen, known as "rosettes" (11). In the succeeding few columns (hours) the rosettes calve short arcs of cells, bowed with their horns towards the anterior, and then these close (and eject excess cells) to form five-cell preclusters (see Figure 4, 11). The most posterior cell will become the founding photoreceptor (the R8), the next anterior pair will later differentiate as R2 and R5, and the most anterior pair will form R3 and R4 (3, 8, 9, 11, 12). The cells that are not included in the preclusters divide one final time, and then form a pool from which the remaining fifteen cells of the ommatidium are recruited, first the final outer photoreceptors (R1 and R6), the final photoreceptor (R7), and then the accessory cells (3, 8, 9, 11, 12). All of these developmental events are driven by positional information generated by cell-cell signaling: there is no information encoded in cell lineage (3, 48).

figure 4

In one eye-disc preparation much of the developmental process is laid out as a staged array. In addition to the ~ two hour inter-column time scale, there is a ~ fifteen minute time scale along one column (11). The first cluster of each column is formed at the eye midline, and is followed at fifteen minute intervals by further clusters, dorsal and ventral to it (11). It is thus possible to time developmental events very precisely by simple examination of the array. As cells differentiate as neurons they express specific antigens and elaborate axons from their basal ends (3, 8, 9, 13, 14). Later they express photoreceptor sub-type specific markers (13-21), and much later terminal functions such as structural components and phototransduction components (opsins, channels, etc., 49, 50-67).

Eye development part II: the molecular signals

The initiation and progression of the furrow is driven by the forward diffusion of Hedgehog (Hh), expressed in precluster cells posterior to the furrow, and is likely to be carried forward by a signal relay that may involve Dpp or other BMP/TGF b homologs (68-81). The hedgehog gene is one of about twenty "segment polarity" genes (82) that act in embryonic segmentation, and then again later in the developing adult structures to specify compartment (lineage) boundaries (83-89). How the eye uses much of the same moleculray circuitry to make a moving wave of development is interesting to us, and we think may be through special mechanisms of hedgehog regulation (see Hedghog project page).

Specification of the preclusters and R8 founder cells in the furrow depends on the focusing of the initially broad expression of transcription factor called Atonal (Ato, 70, 90, 91-95). This focusing depends upon local signaling through the Notch pathway (see below and 93-95, 96). Once the R8 founder cell is specified it expresses a specific surface ligand (Boss, 17, 97, 98, 99), and its maintenance later becomes dependent on signaling mediated by the EGFR via the Ras pathway to the Drosophila ERK homolog (Rolled, see below 100, 101-103). Specification of all the later cell types depends on Ras/ERK signal transduction, stimulated by two currently known Receptor Tyrosine Kinases (RTKs): EGFR and Sevenless (104-121). There are likely to be additional RTK acting in ommatidial assembly. How so many different cell-types can be specified by one ultimate signal (ERK activation to form dp-ERK) is a current focus of several research groups (see EGFR project page).

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