Identification of a gene involved in Snail-mediated Bazooka regulation during epithelial-mesenchymal transition in Drosophila melanogaster

Abstract

Cell-cell adhesions and apical-basal polarity are defining characteristics of epithelial cells that are downregulated during epithelial-mesenchymal transition (EMT), an evolutionarily conserved process that is integral to generation of tissue diversity in morphogenesis, tissue regeneration, and cancer metastasis. Bazooka (Baz, Drosophila homolog of PAR-3) is a polarity protein that is crucial for the establishment and maintenance of cell-cell adhesions and apical-basal polarity in epithelial cells. Previous research has shown that the Snail transcription factor, which drives EMT in many systems, causes displacement of Baz from its subapical position and downregulates Baz in the mesoderm during EMT in Drosophila embryos. We hypothesized that Snail regulates Baz post-transcriptionally through the action of one of its transcriptional target genes. In light of observations in our lab that Drosophila embryos lacking the X chromosome fail to downregulate mesodermal Baz during EMT, we characterized mutant phenotypes of the mesodermal downregulation and subcellular localization of Baz. We then conducted genetic mapping experiments to identify the gene that is responsible for the Snail-mediated regulation of Baz. Herein, we describe our phenotypic characterization and genetic mapping, and discuss the identification of a candidate gene CG14427 that is likely to be the link between Snail and Baz in this pathway. Our findings support emerging evidence that implicates Baz regulation as an important component of the mechanisms of cell polarity loss and cell-cell adhesion loss that are necessary for the progression of EMT.