Dissecting single cell dynamics that coordinate neural crest migration and diversification

研究综述 胚胎发育包括形成由许多 不同的细胞类型，往往起源于不同的位置。因此，细胞迁移和 差异化必须紧密协调，但通常作为独立的研究 流程。在这里，我们使用单细胞基因表达谱的组合， 斑马鱼遗传学和计算模型，以检验迁徙和 分化是协调的。这种协调需要特定的细胞调节器 黏附动力学和细胞-细胞信号传递。我们专注于神经脊细胞，一种暂时性的 胚胎种群在整个身体内迁移，产生大量的 不同的命运。研究这个问题的一个障碍是工具的数量有限 可用于在单个细胞分化时检测它们的过渡状态，并将其与 他们的迁徙行为是精确和定量的。在这里，我们开发了新的 从已知位置和在单细胞中分析基因表达的方法 在活体内追踪它们的运动。我们将分析细胞黏附所需的基因 细胞-细胞信号影响这些过程，并使用计算模型 预测神经脊细胞反应的关键特征。我们预计这样的一个 多学科方法将揭示整合细胞的机制 迁徙和命运。

RESEARCH SUMMARY Embryonic development involves the formation of functional organs comprised of many different cell types, which often originate from different locations. Thus cell migration and differentiation must be tightly coordinated, but are typically studied as independent processes. Here we use a combination of gene expression profiling in single cells, zebrafish genetics and computational models to test the hypothesis that migration and differentiation are coordinated. This coordination requires specific regulators of cell adhesion dynamics and cell-cell signaling. We focus on neural crest cells, a transient embryonic population that migrates throughout the body to give rise to a huge range of different fates. One barrier to studying this problem has been the limited number of tools available to detect transitional states in individual cells as they differentiate and tie this to their migratory behaviors in a precise and quantitative manner. Here we develop new approaches for profiling gene expression in single cells from known locations and tracking their movements in vivo. We will analyze how genes required for cell adhesion and cell-cell signaling influence these processes, and use computational models to predict key features of neural crest cell responses. We expect that such a multidisciplinary approach will reveal insights into the mechanisms that integrate cell migration and fate.