Screening of genes vital for the epithelial homeostasis with Scribble in Drosophila imaginal wing disc morphogenesis

Abstract

The model of Drosophila melanogaster wing imaginal disc has been used to study which growth factors are needed for tissue growth and what are the components for tissue to stop growing when it has reached its proper size. The sack-like structure of the wing disc is composed of epithelial cells and one of the characteristics of such cells is apico-basal polarity (ABP). ABP is a critical factor that coordinates epithelial tissue homeostasis. The disruption of ABP leads to a complete loss of polarity and subsequent neoplasia formation. Scribble (Scrib) is one of the vital proteins that is involved in epithelial polarity determination and maintenance. Recent studies have revealed that the formation of neoplasia derived from local loss of Scrib depends on the copy number of Scrib within the tissue, providing a hypothesis that loss of Scrib-derived neoplasia formation is affected by additional genes having synergy with Scribble. To address this question, a gene screening was performed. The understanding of the hypothetical mechanism of how intercellular alignment occurs and which factors and genes are involved in homeostasis with Scrib has yet to be established. The importance of genes is determined by using deficiency fly lines with deletion in specific genomic regions and the following conditional knockdown of scrib initiated by RNAi mechanism. The screening of previously established candidates allowed to narrow down the genomic region and to test the involvement of one of the potential genes - Neurexin-IV (Nrx-IV). Taken together, this study indicates that the genetic approach is valid and powerful for further investigating molecular mechanisms behind neoplasia/tumor formation.