Transcriptional response to Activating transcription factor 3 (Atf3) activity in the Drosophila eye antenna imaginal disc (EAD) epithelium.. Drosophila melanogaster

Here we describe the transcriptional response to Atf3 expression in the EAD. Atf3 is a cell polarity response gene acting downstream of the membrane-associated Scribble polarity complex. Loss of the neoplastic tumor suppressors Scribble or Dlg1 induces Atf3 expression via aPKC signaling. Using ChIP-seq we have determined that Atf3 targets are enriched for roles in cytoarchitecture. Gain of Atf3 function interferes with organization of the microtubule network, thereby disturbing vesicular trafficking processes including endocytosis, and consequently alters the distribution of key polarity proteins along the apicobasal axis. Conversely, removal of Atf3 from cells lacking Dlg1 suppresses trafficking defects and restores both the normal localization of polarity determinants and epithelial differentiation. These results thus establish loss of polarity as a novel cue that induces Atf3 and demonstrate that gain of Atf3 function drives specific hallmarks of epithelial cells deficient for the Scribble polarity module. Overall design: Examination of mRNA expression following gain of Drosophila Atf3 function in the EAD. Using four biological replicates, RNA from mosaic EAD overexpressing Atf3 (FRT82B atf3) was isolated and single-end sequenced on the Illumina NextSeq 500 instrument at 75 bp read length. FRT82B samples (GSM1591021,GSM1591022,GSM1591023,GSM1591024) from Kuelshammer et al., 2015 Disease Models and Mechanisms (GEO accession number GSE65261) were used as control.