GSE106650
Neuronal target-derived gene activation mediated by widespread use of a BMP-activation element
In Drosophila, efferent neurons gain access to a target-derived BMP signal in the periphery that is required for differentiation and/or synaptic growth and neurotransmission. This requires transcriptional activity of the BMP-activated Smad transcription factors, but the Smad-bound enhancers and BMP-regulated effector genes they control remain unidentified. In the absence of insight into how BMP signaling controls these fundamental aspects of neuronal development and function, here we test whether Smads act directly at widely-deployed archetypal Smad-binding motifs to directly co-regulate batteries of BMP-responsive genes. To target these motifs for analysis, we employed a bioinformatics approach to identify candidate motifs conforming to the consensus 15bp BMP-Activation Element (BMP-AE). After filtering for high conservation and proximity to neuronally-expressed genes, we prioritized 62 BMP-AEs for analysis. Testing the in vivo enhancer activity of 58 genomic fragments containing these BMP-AEs in transgenic reporters, we show that 61% are functional BMP enhancers in diverse motoneuron and neuropeptidergic neuronal populations, and that the BMP-AE motif itself is required for activity. Moreover, 60% of these functional BMP-AEs were located within 20kb of at least one BMP activated gene, as identified by RNAseq analysis. Finally, we show that the BMP-AE motif plays a conserved activator function in the vertebrate nervous system, by electroporation in the developing chick neural tube. Our results provide evidence that BMP signaling controls neuronal development and function by directly coordinating networks of genes through widespread deployment of conserved, consensus Smad-binding motifs. Overall design: RNA sequencing expression profiles of witA12/+ and witA12/B11 Drosophila third instar ventral nerve cords.