Browsing by Author "Fischbach, Lea"

Establishing and maintaining cell polarity is critical to all multicellular organisms. Apicobasal polarity is a type of cell polarity specific to epithelial cells, which is established and maintained by three distinct protein complexes. Among them, the Scribble (Scrib) complex plays a role as a basolateral determinant. Scrib is a scaffold protein with multiple functions, including maintenance of the basolateral polarity of epithelial cells and a tumor suppressor, acting as a regulator of the Hippo signalling, an evolutionarily conserved pathway which controls organ size through regulation of cell proliferation and apoptosis by inhibiting the transcriptional co-activator protein Yorkie (Yki). A recent experiment proposed that Scrib is involved in maintaining tissue homeostasis through relaying apicobasal polarity regulation across the tissue. This mechanism can be used both by normal cells to rescue hypomorphic scrib cells and by loss of scrib cells to spread loss of polarity. The signal is likely related by cell-cell contact and the junctions present in epithelial cells may be involved in this communication. This project aims to identify the genes involved in tissue homeostasis through intercellular alignment of apicobasal polarity together with Scrib. First, a screening protocol was established by studying genetic interactions and tissue structure. Second, a systematic screening was carried out by using deficiency lines of left arm of the third chromosome in Drosophila. Fly stock expressing spatially and temporally controlled scrib RNAi was established and crossed with deficiency lines to identify genes that have synergy with Scrib. The wing discs of the offspring were dissected, imaged, and the phenotypes were sorted into categories according to the degree of overgrowth. Five strong candidates and four candidates with milder phenotype were identified. The results show the screening method is robust and suitable to carry out a finer, single gene level screen of the candidates, as well as screening for additional candidates in the rest of the Drosophila genome. The identified candidates provide new leads to develop the theorical model of intercellular alignment of apicobasal polarity. Understanding how apicobasal polarity is maintained in the dynamic environment of a living organism is important for physiological and pathological conditions. This study provides an important insight into further understanding tissue development and homeostasis.