Proneural function of neurogenic genes in the developing Drosophila eye

Background: Intercellular signals are major determinants of cell fate during development. Certain signals and receptors are important for many different cell-fate decisions, suggesting that cellular responses to similar signals change during development. Few transitions between such distinct cellular responses have been studied. The Drosophila genes Notch and hedgehog function during intracellular signaling at various stages of development. In the specific case of development of the Drosophila eye, expression of the proneural gene atonal is induced in response to Hedgehog signaling and then becomes subject to autoregulation. The receptor protein Notch has previously been reported to function in the selection of single founder photoreceptor cells (R8 cells) by inhibiting atonal expression. On this basis, complete elimination of Notch gene function would be expected to cause neural hyperplasia in the eye. Results: Contrary to expectation, we detect a reduction in neural differentiation both in cells expressing a conditional Notch allele and in those lacking expression of either Notch or its ligand Delta. We show here that Notch signaling acts after the initial Hedgehog-driven expression of atonal to enhance proneural competence of the atonal-expressing cells and also to terminate their response to the Hedgehog signals. This occurs before the Notch induced lateral inhibition of atonal expression within the same cells. Conclusions: Notch has sequentially opposite effects on the same cells, by first promoting and then inhibiting proneural gene function. This apparently paradoxical sequence of events has two possible consequences. Firstly, coupling of alternative cellular responses to the same receptor may prevent them from occurring simultaneously. Secondly, consecutive regulatory processes become temporally coupled, so that these events follow on from each other, without gaps or overlaps.