Escargot and Scratch regulate neural commitment by antagonizing Notch activity in Drosophila sensory organs

During Notch (N)-mediated binary cell fate decisions, cells adopt two different fates according to the levels of N pathway activation: an N_off-dependent or an N_on-dependent fate. How cells maintain these N activity levels over time remains largely unknown. We address this question in the cell lineage that gives rise to the Drosophila mechanosensory organs. In this lineage a primary precursor cell undergoes a stereotyped sequence of oriented asymmetric cell divisions and transits through two neural precursor states before acquiring a neuron identity. Using a combination of genetic and cell biology strategies, we show that Escargot and Scratch, two transcription factors belonging to the Snail superfamily, maintain N_off neural commitment by directly blocking the transcription of N target genes. We propose that Snail factors act by displacing proneural transcription activators from DNA binding sites. As such, Snail factors maintain the N_off state in neural precursor cells by buffering any ectopic variation in the level of N activity. Since Escargot and Scratch orthologs are present in other precursor cells, our findings are fundamental for understanding precursor cell fate acquisition in other systems.