Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Dev Growth Differ. 2021 Dec;63(9):523-535. doi: 10.1111/dgd.12757. Epub 2021 Nov 16.
Lymphatic valves develop from pre-existing endothelial cells through a step-wise process involving complex changes in cell shape and orientation, along with extracellular matrix interactions, to form two intraluminal leaflets. Once formed, valves prevent back-flow within the lymphatic system to ensure drainage of interstitial fluid back into the circulatory system, thereby serving a critical role in maintaining fluid homeostasis. Despite the extensive anatomical characterization of lymphatic systems across numerous genus and species dating back several hundred years, valves were largely thought to be phylogenetically restricted to mammals. Accordingly, most insights into molecular and genetic mechanisms involved in lymphatic valve development have derived from mouse knockouts, as well as rare diseases in humans. However, we have recently used a combination of imaging and genetic analysis in the zebrafish to demonstrate that valves are a conserved feature of the teleost lymphatic system. Here, we provide a historical overview of comparative lymphatic valve anatomy together with recent efforts to define molecular pathways that contribute to lymphatic valve morphogenesis. Finally, we integrate our findings in zebrafish with previous work and highlight the benefits that this model provides for investigating lymphatic valve development.
淋巴瓣膜通过一个逐步的过程从预先存在的内皮细胞发育而来，该过程涉及细胞形状和方向的复杂变化，以及细胞外基质的相互作用，从而形成两个腔内瓣膜。一旦形成，瓣膜可防止淋巴系统中的回流，以确保间质液回流到循环系统，从而在维持液体平衡方面发挥关键作用。尽管数百年来对包括许多属和物种在内的淋巴系统进行了广泛的解剖学描述，但瓣膜在很大程度上被认为是在进化上仅限于哺乳动物。因此，大多数关于淋巴瓣膜发育涉及的分子和遗传机制的见解都来自于小鼠基因敲除，以及人类罕见疾病。然而，我们最近在斑马鱼中结合使用成像和遗传分析来证明瓣膜是硬骨鱼淋巴系统的保守特征。在这里，我们提供了比较淋巴瓣膜解剖学的历史概述，以及最近定义有助于淋巴瓣膜形态发生的分子途径的努力。最后，我们将斑马鱼的研究结果与之前的工作相结合，并强调了该模型在研究淋巴瓣膜发育方面的优势。
