Department of Physics, Syracuse University, Syracuse, New York.
Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, New York.
Biophys J. 2018 Dec 4;115(11):2259-2270. doi: 10.1016/j.bpj.2018.10.028. Epub 2018 Nov 6.
In embryonic development, cell shape changes are essential for building functional organs, but in many cases, the mechanisms that precisely regulate these changes remain unknown. We propose that fluid-like drag forces generated by the motion of an organ through surrounding tissue could generate changes to its structure that are important for its function. To test this hypothesis, we study the zebrafish left-right organizer, Kupffer's vesicle (KV), using experiments and mathematical modeling. During development, monociliated cells that comprise KV undergo region-specific shape changes along the anterior-posterior axis that are critical for KV function: anterior cells become long and thin, whereas posterior cells become short and squat. Here, we develop a mathematical vertex-like model for cell shapes that incorporates both tissue rheology and cell motility and constrain the model parameters using previously published rheological data for the zebrafish tailbud as well as our own measurements of the KV speed. We find that drag forces due to dynamics of cells surrounding KV could be sufficient or work in concert with previously identified mechanisms to drive KV cell shape changes during KV development. More broadly, these results suggest that cell shape changes during embryonic development and beyond could be driven by dynamic forces not typically considered in models or experiments.
在胚胎发育过程中，细胞形状的变化对于构建功能性器官至关重要，但在许多情况下，精确调节这些变化的机制仍不清楚。我们提出，器官在周围组织中运动产生的类似流体的阻力可能会导致其结构发生变化，而这些变化对于其功能很重要。为了验证这一假设，我们使用实验和数学建模来研究斑马鱼左右组织者，即 Kupffer 泡（KV）。在发育过程中，构成 KV 的单纤毛细胞沿着前后轴经历特定区域的形状变化，这对于 KV 的功能至关重要：前部细胞变得细长，而后部细胞变得短而粗。在这里，我们开发了一种用于细胞形状的顶点样数学模型，该模型同时考虑了组织流变学和细胞运动，并使用先前发表的斑马鱼尾芽的流变学数据以及我们自己对 KV 速度的测量来约束模型参数。我们发现，由于围绕 KV 的细胞的动力学产生的阻力可能足以或与先前确定的机制协同作用，以在 KV 发育过程中驱动 KV 细胞形状的变化。更广泛地说，这些结果表明，胚胎发育过程中和之后的细胞形状变化可能是由通常在模型或实验中不考虑的动态力驱动的。
