Understanding the mechanisms involved in tissue reorganization and organ formation are fundamental questions that are of particular interest to those studying epithelial morphogenesis. Model organisms such as Drosophila melanogaster have been instrumental in identifying key components required for cellular processes that are critical for tissue morphogenesis as a whole. These include cell fate specification, cell shape change, cell growth and cell migration. The Rho subfamily of small GTPases Rho, Rac and Cdc42, are master regulators of actin cytoskeletal dynamics and the well-characterized Rac/Cdc42 effector kinase Pak has been implicated in morphogenesis of epithelia both in mammalian cell culture as well as Drosophila development. Drosophila oogenesis is a highly favourable system for studying epithelial morphogenesis and differentiation of epithelia from a stem cell. Newly formed germline cysts become encapsulated by follicle cells that arise from follicle stem cells (FSCs) to form egg chambers. This study on Pak function during oogenesis, combined with the work of others, has opened the door to our understanding of how the FSC and its niche produce a simple yet very organized epithelium. Pak appears to be required during early stages of oogenesis at or around the time point at which FSCs and/or their niches are specified. Loss of Pak during early stages of oogenesis leads to a novel side-by-side egg chamber phenotype with pak mutant germaria having duplicated FSC niches, implicating Pak in FSC niche formation. This work has led to a model for stem cell niche formation that may be broadly applicable. Later in oogenesis Pak is required for the polarized organization of the basal F-actin in follicle cells, which drives egg chamber elongation. Further investigation of Pak’s role has demonstrated that it acts antagonistically to the Rho1-activated actomyosin contractility pathway in regulation of this F-actin. The basal F-actin of the follicle cells is similarly organized as the stress fibres of mammalian cells and insights gained from this work are likely to be relevant to understanding regulation of the mammalian cytoskeleton. Overall this work has revealed new roles for Pak in epithelial development.
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Thesis advisor: Harden, Nicholas
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