PRONEURAL GENE SELF-STIMULATION IN NEURAL PRECURSORS - AN ESSENTIAL MECHANISM FOR SENSE ORGAN DEVELOPMENT THAT IS REGULATED BY NOTCH SIGNALING

To learn about the acquisition of neural fate by ectodermal cells, we have analyzed a very early sign of neural commitment in Drosophila, na mely the specific accumulation of achaete-scute complex (AS-C) proneur al proteins in the cell that becomes a sensory organ mother cell (SMC) . We have characterized an AS-C enhancer that directs expression speci fically in SMCs, This enhancer promotes Scute protein accumulation in these cells, an event essential for sensory organ development in the a bsence of other BS-C genes. Interspecific sequence comparisons and sit e-directed mutagenesis shaw the presence of several conserved motifs n ecessary for enhancer action, some of them binding sites for proneural proteins. These and other data indicate that the enhancer mediates sc ute self-stimulation, although only in the presence of additional acti vating factors, which most likely interact with conserved motifs remin iscent of NF-kappa B-binding sites. Cells neighboring the SMC do not a cquire the neural fate because the Notch signaling pathway effectors, the Enhancer of split bHLH proteins, block this proneural gene self-st imulatory loop, possibly by antagonizing the action on the enhancer of the NF-kappa B-like factors or the proneural proteins. These data sug gest a mechanism for SMC committment.