LAUSR

The development of a single-celled zygote to a multicellular organism requires the rapid yet controlled proliferation of cells. Both cell number and cell size are meticulously regulated in order to form complex tissues and organs. Cell division rate is fundamental for determining cell number and size. Mitosis is a critical process in tissue growth and cell biological research that remains to be fully understood, especially within a multicellular tissue environment. This project aims to investigate how mitosis is regulated in complex epithelial structures found during organ development and how mitosis is influenced by changing tissue structure. Mitotic divisions will be studied within the highly proliferative epithelial tissue, the Drosophila wing disc. The wing disc is an intermediatelength pseudostratified epithelium (PSE). PSE is found widely in early organ development, and notably during neural tube to neocortex formation. To undergo mitosis within PSE, a nucleus must translocate from the basal to the apical surface prior to mitotic cell rounding, a process called Inter-kinetic Nuclear Migration (IKNM). The machinery that drives IKNM differs depending on the height of the epithelium. Short epithelia depend on actomyosin, whilst tall epithelia utilise microtubule transport and motor proteins. These mechanisms may cooperate in intermediate PSE but the regulation of IKNM remains to be elucidated. How tissue architecture affects IKNM is the main focus of this project. The developmental increase in cell compaction and cell height within the Drosophila wing disc provides an ideal model system to study this question. Varying cell and tissue morphology may influence aspects of IKNM to regulate tissue growth. The characteristic folds of the wing disc provide regions of positive and negative curvature to observe the effects of opposing apical surface on IKNM. Furthermore, the powerful genetic tools provided by Drosophila will allow novel regulators of IKNM to be identified.