A Homeobox Transcription Factor Scarecrow (SCRO) Negatively Regulates Pdf Neuropeptide Expression through Binding an...

In Drosophila, transcriptional feedback loops contribute to intracellular timekeeping mechanisms responsible for daily rhythms. Pigment-dispersing factor (PDF) is the major neuropeptide produced by latero-ventral neurons (LN_vs) that function as a central pacemaker for circadian locomotor activity rhythms. PDF synchronizes other clock neurons thereby playing an essential role in the maintenance and coordination of circadian locomotor rhythms. However, the underlying molecular mechanism of the LN_vs-specific Pdf expression is not well understood. Here, using Pdf promoter-bashing experiment, we identified a cis-acting Pdf regulatory element (PRE) that is sufficient for driving Pdf expression in the LN_vs. We have also identified a homeobox transcription factor, scarecrow (SCRO), as a direct binding factor to PRE. Furthermore, transgenic expression of scro in the clock neurons abolished Pdf expression and circadian locomotor activity rhythms, and such repressive function requires DNA-binding homeodomain, but none of the other conserved domains. scro is predominantly expressed in the optic lobe and various clusters of cells in other areas of the central nervous system. A homozygous scro-null mutant generated by CRIPSR is lethal during embryonic and early larval development, suggesting that scro plays a vital role during early development.