Collective dynamics in cell clusters

摘要 这项工作将联合收割机的实验和理论相结合，以促进定量的了解动物 配子发生我们使用果蝇作为一种遗传模式生物，非常适合于定量研究。 跨学科的研究，并侧重于生殖生物学的两个进化保守的方面。首先，鸡蛋 并且大体积的早期胚胎需要用于协调细胞质过程的有效手段。研究 多个实验系统表明，大细胞中的这种协调依赖于大规模的流体动力学 流速可达100 s nm/s，可介导细胞质的快速混合和运输。 件.我们的目标1研究了果蝇卵子发生中的一个关键点上的这种流动， 流由在皮层锚定的微管阵列上行走的装载货物的驱动蛋白马达驱动。我们 将使用计算建模和实时成像系统地测试最近的理论，根据该理论， 细胞质流动自发出现，通过流体动力学耦合的皮质锚定， 微管其次，果蝇和人类的配子发生都是从细胞周期的形成开始的 原始生殖细胞（Primordial germ cells，PCS）PGC数量的定量控制对生物体的生育力至关重要 以及避免生殖系肿瘤。目的2研究果蝇PGCs数量的定量调控 胚胎，其中PGC由极细胞的有限分裂形成，极细胞是胚胎中形成的第一个真正的细胞。 我们将使用实时成像来表征极细胞谱系的统计学特征，并检验控制极细胞谱系的假设。 PGC数可以用一个模型来解释，在这个模型中，有丝分裂时钟慢慢地偏离振荡状态。 考虑到细胞质流动的普遍性和PGC调控的保守机制，我们的结果将 通过提供发育和生殖生物学基本问题的答案而产生广泛的影响。

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.