Differential activity of EWG transcription factor isoforms identifies a subset of differentially regulated genes important for synaptic growth regulation.

The vast majority of genes in the human genome is alternatively spliced. The functional consequences of this
type of post-transcriptional gene regulation that is particularly prominent in the brain, however, remains
largely elusive. Here we analyzed the role of alternative splicing in the transcription factor erect wing (ewg) in
Drosophila and dissect its function through differential rescue with transgenes encoding different isoforms.
Transgenes expressing the SC3 ORF isoform fully rescue viability and synaptic growth defects. In contrast,
transgenes expressing the ΔDJ isoform, that lack exons D and J, have a lower activity as inferred from their
expression levels and exert reduced rescue of viability and synaptic growth defects. By comparison of the gene
expression profile of ewgl1 mutants rescued either by the SC3 ORF or the ΔDJ transgene, we identified a set of
genes whose expression is exclusively restored by the SC3 isoform. These genes are mostly involved in
regulating gene expression while a core function of EWG is indicated by the regulation of metabolic genes by
both isoforms. In conclusion, we demonstrated that differential rescue with different isoform encoding
transgenes of the transcription factor EWG identifies a unique set of genes associated with synaptic growth
regulation.