Screening for novel components of intercellular network involved in growth and homeostasis of Drosophila wing imaginal disc

Abstract

The apicobasal polarity is an essential attribute of the epithelial tissue. The disruption of the apicobasal polarity is an essential attribute of the epithelial tissue. The disruption of po- larity results in the loss of homeostasis and functionality of the tissue. The major apico- basal polarity determinant, tumour suppressor gene scrib, was found to be regulated by in- tercellular communications. When the conditional knockdown of scrib was introduced by patched-Gal4 driver, the progressive loss of polarity from the targeted cells to the neigh- bouring, healthy cells was observed. Recent studies further revealed that the interactions of Scrib with septate junctions components and the α-Catenin are crucial for sustaining inter- cellular communications. These findings suggest that a complex molecular network is in- volved in Scrib-mediated tissue homeostasis. To understand what molecules are needed to interact with Scrib, what mechanisms are utilized for mediating cell-cell communications for epithelial tissue development, and how they involve in the development of pathogenic processes, e.g., neoplasia formation, identification of the genes interacting with Scrib ap- pears to be important. In this thesis project, the Drosophila melanogaster wing imaginal disc was utilized as a model to explore potential gene candidates, interacting synergistically with scrib to main- tain intercellular mechanisms during epithelial development. To achieve this goal, a two- step genetic screening was used by combining conditional RNAi knockdown of scrib and chromosome deficiency lines of the third chromosome in Drosophila in a sensitized back- ground (heterozygous for candidate gens). The primary screening involved ten deficiency stocks that accounted for about 10% of the right arm of the third chromosome. Subse- quently, a secondary screening was performed to narrow down the locus of deficiency by employing multiple deficiency lines that overlap with the candidate deficiency line from the primary screening. The results provide one strong deficiency line candidate, composed of 10 coding genes, that may have synergy with scrib.