The Scalloped and Nerfin-1 Transcription Factors Cooperate to Maintain Neuronal Cell Fate

The ability of cells to stably maintain their fate is governed by specific transcription regulators. Here, we show that the Scalloped (Sd) and Nervous fingers-1 (Nerfin-1) transcription factors physically and functionally interact to maintain medulla neuron fate in the Drosophila melanogaster CNS. Using Targeted DamID, we find that Sd and Nerfin-1 occupy a highly overlapping set of target genes, including regulators of neural stem cell and neuron fate, and signaling pathways that regulate CNS development such as Notch and Hippo. Modulation of either Sd or Nerfin-1 activity causes medulla neurons to dedifferentiate to a stem cell-like state, and this is mediated at least in part by Notch pathway deregulation. Intriguingly, orthologs of Sd and Nerfin-1 have also been implicated in control of neuronal cell fate decisions in both worms and mammals. Our data indicate that this transcription factor pair exhibits remarkable biochemical and functional conservation across metazoans. Vissers et al. report that the Scalloped and Nerfin-1 transcription factors physically and functionally interact to maintain medulla neuron fate in the Drosophila CNS. Identification of their genome-binding profiles reveal that these transcription factors regulate neuron fate, at least in part, by modulating Notch signaling.