Collective dynamics in cell clusters

点击翻译按钮获取中文摘要

Abstract The proposed work will combine experiments and theory to advance quantitative understanding of animal gametogenesis. We use Drosophila as a genetic model organism that is highly suitable for quantitative interdisciplinary research and focus on two evolutionarily conserved aspects of reproductive biology. First, eggs and early embryos of large volumes require efficient means for coordinating cytoplasmic processes. Studies in multiple experimental systems indicate that such coordination in large cells relies on large-scale hydrodynamic flows, which reach the speeds of 100s nm/s and can mediate rapid mixing and transport of cytoplasmic components. Our Aim 1 investigates such flows at a critical point in Drosophila oogenesis, where cytoplasmic streaming is driven by cargo-loaded kinesin motors walking on arrays of cortically anchored microtubules. We will use computational modeling and live imaging to systematically test a recent theory according to which cytoplasmic streaming emerges spontaneously, through hydrodynamic coupling of cortically anchored microtubules. Second, gametogenesis in both Drosophila and humans starts with the formation of cell-cycle arrested primordial germ cells (PCSs). Quantitative control of PGC numbers is essential for organismal fertility and for avoiding germline tumors. Aim 2 will investigate quantitative control of PGCs numbers in Drosophila embryos, where PGCs are formed by limited divisions of the pole cells, the first true cells to form in the embryo. We will use live imaging to characterize statistics of pole cell lineages and test the hypothesis that control of PGC numbers can be explained using a model in which a mitotic clock slowly drifts out of an oscillatory regime. Given the ubiquitous nature of cytoplasmic flows and conserved mechanisms of PGC regulation, our results will have broad impact by providing answers to fundamental questions of developmental and reproduction biology.