Pancreatic islets, discrete microorgans embedded within the exocrine pancreas, contain beta cells which are critical for glucose homeostasis. Loss or dysfunction of beta cells leads to diabetes, a disease with expanding global prevalence, and for which regenerative therapies are actively being pursued. Recent efforts have focused on producing mature beta cells in vitro, but it is increasingly recognized that achieving a faithful three-dimensional islet structure is crucial for generating fully functional beta cells. Our current understanding of islet morphogenesis is far from complete, due to the deep internal location of the pancreas in mammalian models, which hampers direct visualization. Zebrafish is a model system well suited for studies of pancreas morphogenesis due to its transparency and the accessible location of the larval pancreas. In order to further clarify the cellular mechanisms of islet formation, we have developed new tools for in vivo visualization of single-cell dynamics. Our results show that clustering islet cells make contact and interconnect through dynamic actin-rich processes, move together while remaining in close proximity to the duct, and maintain high protrusive motility after forming clusters. Quantitative analyses of cell morphology and motility in 3-dimensions lays the groundwork to define therapeutically applicable factors responsible for orchestrating the morphogenic behaviors of coalescing endocrine cells.

胰腺胰岛是嵌入外分泌胰腺内的离散微器官，含有对葡萄糖体内稳态至关重要的β细胞。β细胞的丢失或功能异常会导致糖尿病，这种疾病的全球患病率正在扩大，并且正在积极地寻求再生疗法。最近的努力集中在生产成熟的β细胞体外，但人们越来越认识到，实现忠实的三维胰岛结构对于生成功能齐全的β细胞至关重要。由于胰脏在哺乳动物模型中的内部位置较深，妨碍了直接观察，因此我们目前对胰岛形态发生的了解还远远不够。斑马鱼的透明性和幼体胰腺的可及位置，使其非常适合研究胰腺形态发生的模型系统。为了进一步阐明胰岛形成的细胞机制，我们开发了新的工具用于体内可视化单细胞动力学。我们的研究结果表明，聚集的胰岛细胞通过动态富含肌动蛋白的过程进行接触和相互连接，在保持紧密靠近导管的状态下一起移动，并在形成聚集后保持较高的运动力。对3维细胞形态和运动性的定量分析奠定了基础，以定义负责协调凝聚内分泌细胞形态发生行为的治疗适用因素。