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 ma ny different cell-fate decisions, suggesting that cellular responses t o similar signals change during development, Few transitions between s uch distinct cellular responses have been studied, The Drosophila gene s Notch and hedgehog function during intracellular signaling at variou s stages of development. In the specific case of development of the Dr osophila eye, expression of the proneural gene atonal is induced in re sponse to Hedgehog signaling and then becomes subject to autoregulatio n, 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 N otch gene function would be expected to cause neural hyperplasia in th e eye. Results: Contrary to expectation, we detect a reduction in neur al 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-driv en 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 at onal expression within the same cells. Conclusions: Notch has sequenti ally opposite effects on the same cells, by first promoting and then i nhibiting proneural gene function. This apparently paradoxical sequenc e of events has two possible consequences, Firstly, coupling of altern ative cellular responses to the same receptor may prevent them from oc curring simultaneously. Secondly, consecutive regulatory processes bec ome temporally coupled, so that these events follow on from each other , without gaps or overlaps.