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 signalling 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, orthologues 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. DamID-seq on CNSs from wandering third instar Drosophila larvae expressing Dam control, Dam-Sd or Dam-Nerfin-1 transgenes driven by GMR31H08-Gal4 (two replicates each). ATACseq and RNAseq on FACS sorted wildtype Nerfin-GFP expressing neurons (3 replicates each).