The Drosophila Dpp/BMP signaling directly regulates dpp transcription for optimal ligand dosage

Precise control of morphogen dosage in the source is essential for establishing developmental patterning and maintaining signaling stability. Here, we demonstrate that in Drosophila wing imaginal discs, the Dpp/BMP signaling modulates its ligand Dpp (Decapentaplegic) expression through direct transcriptional auto-regulation. The results show that reduction of Dpp/BMP signaling upregulates dpp transcription, whereas enhanced signaling represses it. This transcriptional negative feedback mechanism primarily depends on the BMP-Silencer-Element (BMP-SE) complex binding to the BMP-SE motifs at the dpp downstream distal cis-regulatory region. We validated this mechanism through BMP-SE complex interference and BMP-SE motif disruption assays. Our findings extend the morphogen source-sink theory by uncovering that the Dpp/BMP signaling pathway dynamically balances Dpp dosage via transcriptional auto-modulation, thereby ensuring optimal ligand production for signaling homeostasis.