CtBP is required for proper development of peripheral nervous system in Drosophila.

C-terminal binding protein (CtBP) is an evolutionarily and functionally conserved transcriptional corepressor known to integrate diverse signals to regulate transcription. Drosophila CtBP (dCtBP) regulates tissue specification and segmentation during early embryogenesis. Here, we investigated the roles of dCtBP during development of the peripheral nervous system (PNS). Our study includes a detailed quantitative analysis of how altered dCtBP activity affects the formation of adult mechanosensory bristles. We found that dCtBP loss-of-function resulted in a series of phenotypes with the most prevalent being supernumerary bristles. These dCtBP phenotypes are more complex than those caused by Hairless, a known dCtBP-interacting factor that regulates bristle formation. The emergence of additional bristles correlated with the appearance of extra sensory organ precursor (SOP) cells in earlier stages, suggesting that dCtBP may directly or indirectly inhibit SOP cell fates. We also found that development of a subset of bristles was regulated by dCtBP associated with U-shaped through the PxDLS dCtBP-interacting motif. Furthermore, the double bristle with sockets phenotype induced by dCtBP mutations suggests the involvement of this corepressor in additional molecular pathways independent of both Hairless and U-shaped. We therefore propose that dCtBP is part of a gene circuitry that controls the patterning and differentiation of the fly PNS via multiple mechanisms.