Department of Molecular Biology, Princeton University, Princeton, NJ, USA; The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ, USA; The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA; Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, NY, USA.
Curr Biol. 2022 Apr 25;32(8):1861-1868.e7. doi: 10.1016/j.cub.2022.02.059. Epub 2022 Mar 14.
Gastrulation movements in all animal embryos start with regulated deformations of patterned epithelial sheets, which are driven by cell divisions, cell shape changes, and cell intercalations. Each of these behaviors has been associated with distinct aspects of gastrulation and has been a subject of intense research using genetic, cell biological, and more recently, biophysical approaches. Most of these studies, however, focus either on cellular processes driving gastrulation or on large-scale tissue deformations. Recent advances in microscopy and image processing create a unique opportunity for integrating these complementary viewpoints. Here, we take a step toward bridging these complementary strategies and deconstruct the early stages of gastrulation in the entire Drosophila embryo. Our approach relies on an integrated computational framework for cell segmentation and tracking and on efficient algorithms for event detection. The detected events are then mapped back onto the blastoderm shell, providing an intuitive visual means to examine complex cellular activity patterns within the context of their initial anatomic domains. By analyzing these maps, we identified that the loss of nearly half of surface cells to invaginations is compensated primarily by transient mitotic rounding. In addition, by analyzing mapped cell intercalation events, we derived direct quantitative relations between intercalation frequency and the rate of axis elongation. This work is setting the stage for systems-level dissection of a pivotal step in animal development.
所有动物胚胎的原肠运动都始于有规律的图案化上皮片的变形，这些变形由细胞分裂、细胞形状变化和细胞插入驱动。这些行为中的每一种都与原肠运动的不同方面有关，并且一直是使用遗传、细胞生物学以及最近的生物物理方法进行深入研究的主题。然而，这些研究中的大多数要么侧重于推动原肠运动的细胞过程，要么侧重于大规模的组织变形。显微镜和图像处理的最新进展为整合这些互补观点创造了独特的机会。在这里，我们朝着弥合这些互补策略的方向迈出了一步，对整个果蝇胚胎的早期原肠运动进行了解构。我们的方法依赖于用于细胞分割和跟踪的集成计算框架，以及用于事件检测的高效算法。然后将检测到的事件映射回胚盘壳上，提供了一种直观的视觉手段，可在其初始解剖结构域的背景下检查复杂的细胞活动模式。通过分析这些图谱，我们发现近一半的表面细胞通过内陷丢失，主要由短暂的有丝分裂圆形化来补偿。此外，通过分析映射的细胞插入事件，我们推导出了插入频率与轴伸长率之间的直接定量关系。这项工作为动物发育关键步骤的系统水平剖析奠定了基础。
