Notch signalling and the initiation of neural development in the Drosophila eye

Neural determination in the Drosophila eye occurs progressively. A diffusib le signal, Dpp, causes undetermined cells first to adopt a 'pre-proneural' state in which they are primed to start differentiating. A second signal is required to trigger the activation of the transcription factor Atonal, whi ch causes the cells to initiate overt photoreceptor neurone differentiation . Both Dpp and the second signal are dependent on Hedgehog (Hh) signalling. Previous work has shown that the Notch signalling pathway also has a prone ural role in the eye (as well as a later, opposite function when it restric ts the number of cells becoming photoreceptors - a process of lateral inhib ition). It is not clear how the early proneural role of Notch integrates wi th the other signalling pathways involved. We provide evidence that Notch a ctivation by its ligand Delta is the second Hh-dependent signal required fo r neural determination. Notch activity normally only triggers Atonal expres sion in cells that have adopted the pre-proneural state induced by Dpp. We also report that Notch drives the transition from pre-proneural to proneura l. by downregulating two repressors of Atonal: Hairy and Extramacrochaetae.