Robust specification of sensory neurons by dual functions of charlatan, a Drosophila NRSF/REST‐like repressor of extramacrochaetae and hairy

Sensory bristle formation in Drosophila is a well‐characterized system for studying sensory organ development at the molecular level. The master proneural genes of the achaete‐scute (ac‐sc) complex, which encode basic‐helix‐loop‐helix (bHLH) transcription factors, are necessary and sufficient for sensory bristle formation. charlatan (chn) was originally identified as a transcriptional activator of ac‐sc gene expression through interaction with its enhancer, an activity that promotes sensory bristle development. In contrast, Chn was also identified as a functional homologue of mammalian neuron‐restrictive silencing factor or RE1 silencing transcription factor (NRSF/REST), an important transcriptional repressor during vertebrate neurogenesis and stem cell development that acts through epigenetic gene silencing. Here, we report that Chn acts as a repressor of extramacrochaetae (emc) and hairy, molecules that inhibit ac‐sc expression. This double‐negative mechanism, together with direct activation via the achaete enhancer, increases expression of achaete and ensures robust development of sensory neurons. A mutation in the C‐terminal repressor motif of Chn, which causes Chn to lose its repression activity, converted Chn to an activator of emc and hairy, suggesting that Chn is a dual functional regulator of transcription. Because chn‐like sequences are found among arthropods, regulation of neuronal development by Chn‐like molecules may be widely conserved.