A low affinity <i>cis</i>-regulatory BMP response element restricts target gene activation to subsets of Drosophila neurons.

Abstract

Retrograde BMP signaling and canonical pMad/Medea-mediated transcription regulate diverse target genes across subsets of <i>Drosophila</i> efferent neurons, to differentiate neuropeptidergic neurons and promote motor neuron terminal maturation. How a common BMP signal regulates diverse target genes across many neuronal subsets remains largely unresolved, although available evidence implicates subset-specific transcription factor codes rather than differences in BMP signaling. Here we examine the <i>cis-</i>regulatory mechanisms restricting BMP-induced <i>FMRFa</i> neuropeptide expression to Tv4-neurons. We find that pMad/Medea bind at an atypical, low affinity motif in the <i>FMRFa</i> enhancer. Converting this motif to high affinity caused ectopic enhancer activity and eliminated Tv4-neuron expression. In silico searches identified additional motif instances functional in other efferent neurons, implicating broader functions for this motif in BMP-dependent enhancer activity. Thus, differential interpretation of a common BMP signal, conferred by low affinity pMad/Medea binding motifs, can contribute to the specification of BMP target genes in efferent neuron subsets.