Background: Receptors of the Notch family affect the determination of many cell types. In the Drosophila eye, Notch antagonises the basic helix-loop-helix (bHLH) protein atonal, which is required for R8 photoreceptor determination. Similar antagonism between Notch and proneural bHLH proteins regulates most neural cell determination, however, it is uncertain whether the mechanisms are similar in all cases. Here, we have analyzed the sensitivity of atonal expression to Notch signalling using a temperature-sensitive Notch allele, by the expression of activated Notch or of the ligand Serrate, and by monitoring expression of the atonal-dependant gene scabrous and of the Notch-dependent Enhancer of split genes.
Results: The atonal expression pattern evolves from general "prepattern' expression, through transient "intermediate groups' to R8 precursor-specific expression. Successive phases of atonal expression differ in sensitivity to Notch. Prepattern expression of atonal is not inhibited. Inhibition begins at the intermediate group stage, corresponding to the period when atonal gene function is required for its own expression. At the transition to R8 cell-specific expression, Notch is activated in all intermediate group cells except the R8 cell precursor. R8 cells remain sensitive to inhibition in columns 0 and 1, but become less sensitive thereafter; non-R8 cells do not require Notch activity to keep atonal expression inactive. Thus, Notch signaling is coupled to atonal repression for only part of the atonal expression pattern. Accordingly, the Enhancer-of-split m delta protein is expressed reciprocally to atonal at the intermediate group and early R8 stages, but is expressed in other patterns before and after.
Conclusions: In eye development, inhibition by Notch activity is restricted to specific phases of proneural gene expression, beginning when prepattern decays and is replaced by autoregulation. We suggest that Notch signalling inhibits atonal autoregulation, but not expression by other mechanisms, and that a transition from prepattern to autoregulation is necessary for patterning neural cell determination. Distinct neural tissues might differ in their proneural prepatterns, but use Notch in a similar mechanism.