Collective dynamics in cell clusters

项目摘要 这项研究将促进对细胞团动力学的机理理解 具有稳定的细胞间胞质桥。这类多细胞系统被认为具有 在多细胞生物出现的过程中发挥了作用，并在今天发挥着关键作用 有机体通过细胞质桥的细胞间运输产生了丰富的功能性 巨大的集体效应。理解这些效应起源的一个关键障碍是 目前缺乏可定量研究的易操作的实验系统。我们的研究 将使用果蝇卵子发生，一个实验系统，提供无与伦比的机会， 定量研究。该系统依赖于两种类型的具有细胞质桥的细胞簇： 包含未来卵母细胞和15个保育细胞的生殖细胞源性细胞簇，以及体细胞簇 在覆盖生殖细胞群的上皮中。我们的研究发现了集体动力学 在两种组织类型中。首先，我们发现生殖细胞群中的细胞以定义的群体生长， 通过集群的连通性。目标1检验了这一增长模式取决于 在集群内的细胞间运输，并反映了内复制细胞的同步动力学 自行车.第二，我们发现体细胞团显示出很强的克隆优势， 在发育生长过程中通常观察到，但了解甚少的影响。目标2测试 假设克隆优势出现的时空协调的结果， 有丝分裂细胞周期我们的工作使用实时成像和计算建模来调查 涌现动力学在一类重要的多细胞系统。由于无处不在的性质， 细胞簇具有稳定的胞质桥，我们的研究结果将产生广泛的影响。

PROJECT SUMMARY The proposed research will advance the mechanistic understanding of dynamics in cell clusters with stable intercellular cytoplasmic bridges. This class of multicellular systems is thought to have played a role during the emergence of multicellularity and serves critical functions in present day organisms. Intercellular transport through cytoplasmic bridges gives rise to a wealth of functionally significant collective effects. One key obstacle in understanding the origins of these effects is the current lack of tractable experimental systems that can be studied quantitatively. Our research will use Drosophila oogenesis, an experimental system that provides unmatched opportunities for quantitative studies. This system relies on two types of cell clusters with cytoplasmic bridges: a germline-derived cluster containing the future oocyte and 15 nurse cells, and somatic cell clusters in the epithelium that envelops the germline cluster. Our research identified collective dynamics in both tissue types. First, we discovered that cells in the germline cluster grow in groups defined by the cluster's connectivity. Aim 1 tests the hypothesis that this growth pattern depends on intercellular transport within the cluster and reflects synchronized dynamics of endoreplication cell cycles. Second, we showed that somatic cell clusters display strong clonal dominance, a commonly observed, yet poorly understood effect during developmental growth. Aim 2 tests the hypothesis that clonal dominance emerges as a consequence of spatiotemporal coordination of mitotic cell cycles. Our work uses live imaging and computational modeling to investigate emergent dynamics in an important class of multicellular systems. Given the ubiquitous nature of cell clusters with stable cytoplasmic bridges, results of our studies will have broad impact.