Neural determination in the Drosophila eye

During the development of multicellular organisms the specification of cells in a complex pattern depends largely on intercellular signalling. Among the best known intercellular signalling pathways is that triggered by the transmembrane receptor Notch (Artavanis-Tsakonas et al., 1999). Notch signalling defines an evolutionarily conserved pathway that is involved in multiple decisions during Drosophiladevelopment. Like other pathways, the outcome of Notch signalling is dependent on the context of the signalling event. This multiplicity of functions is well illustrated in the Drosophila eye, where Notch signalling has successive roles in promoting and inhibiting neural differentiation (Cagan and Ready, 1989; Baker et al., 1990; Parks et al., 1995; Baker et al., 1996; Baker and Yu, 1997; Li and Baker, 2001). Drosophila has a compound eye comprising about 750 ommatidia that form a regular hexagonal array. At the beginning of the third larval instar, a groove known as the morphogenetic furrow begins to sweep anteriorly across the eye imaginal disc. This furrow marks the start of overt neural differentiation, although some markers are expressed a little anterior to the furrow (Ready et al., 1976). The photoreceptors develop in a stereotyped order behind the furrow, first the R8 photoreceptor, followed by the subsequent recruitment of the other photoreceptors from the surrounding undetermined cells (Tomlinson, 1985; Tomlinson and Ready, 1987; Freeman, 1997). The earliest manifestation of neural differentiation is the expression of the proneural bHLH transcription factor Atonal, upon which R8 specification depends (Jarman et al., 1994; Jarman et al., 1995). Atonal is first expressed in a weak uniform stripe of cells in front of the morphogenetic furrow; this stripe is then upregulated and refined into proneural clusters of cells expressing high levels of Atonal and from these, smaller groups of 2-3 cells, the ‘R8 equivalence groups’, emerge. Finally, the expression of Atonal is restricted to the single cell in each cluster, which will become the R8 photoreceptor (Jarman et al., 1994; Jarman et al., 1995; Baker et al., 1996; Dokucu et al., 1996; Baonza et al., 2001). Notch signalling is required for successive steps of R8 determination, specifically in the regulation of Atonal (Baker t al., 1990; Parks et al., 1995; Baker et al., 1996; Dokucu et al., 1996; Baker and Yu, 1997; Baker and Yu, 1998; Li and Baker, 2001). At first, Notch promotes neural differentiation; later it inhibits it. Consequently, the phenotype of Notch loss of function varies with time. When the function of Notch is completely removed from very early stages, neural differentiation does not occur. Similar results with loss of the Notch ligand Delta (Dl), but not with the alternative ligand Serrate (Ser), indicates an early proneural function of Delta-toNotch signalling (Baker and Yu, 1997; Ligoxygakis et al., 1998; Li and Baker, 2001). Conversely, later loss of Notch function, once Atonal expression is refined to proneural clusters, causes excess R8s to form, indicating a function for 3889 Development 128, 3889-3898 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV5938