Stem cell aging and the control of abscission

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): Our tissues inexorably decline during aging. A cause of this is intrinsic changes to the stem cells responsible for tissue homeostasis, or changes in the niche regulating stem cell activity. To explore potential links between cytoskeletal function and aging, there can be great advantage to studying a tissue that has already contributed fundamentally to our understanding of the impact of aging on stem cell function. The Drosophila testis is such a tissue, as germline stem cells (GSCs) have been shown to age, and both intrinsic and extrinsic regulators have been defined. To maintain tissue homeostasis, stem cells must exercise tight spatial and temporal control over daughter cell production. Thus, we have focused on abscission, the last step of cytokinesis, involving the complete separation of daughter cells. Abscission is a key point of regulation generally during cytokinesis, and microtubule and f-actin cytoskeletal dynamics play seminal roles during this process. Abscission has been difficult to image in vivo, but we have been successful using simultaneous imaging of Actin and Myosin II. Our analysis shows that abscission is dramatically delayed in GSCs, even after the contractile ring and the midbody microtubules are disassembled. Surprisingly, a new, filamentous actin-enriched structure succeeds the contractile ring, and serves to stabilize the midbody. We define a regulatory circuit controlling this novel cytoskeletal feature, as well as controls by Aurora B Kinase. Lastly, we find that aging significantly affects abscission, opening up this system to the study of aging and the cytoskeleton. Due to the ease of genetic and pharmacological manipulations, along with the well-characterized behavior of GSCs at steady state and upon aging, the Drosophila testis provides an ideal system in which to study the temporal dynamics, genetic control and roles for cytoskeletal components in abscission events. Here, we test for potential causative links between cytoskeletal control over abscission and aging within this adult stem cell population.