Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
Dev Dyn. 2010 Jul;239(7):2128-35. doi: 10.1002/dvdy.22328.
Lymphangiogenesis induced during tumor growth contributes to metastasis. Genetic and chemical screens using the zebrafish model have the potential to enhance our understanding of lymphangiogenesis, and lead to the discovery of pharmacological agents with activity in the lymphatic system. Large-scale screening of lymphatic development in the whole zebrafish embryo requires a specific lymphatic endothelial cell marker. We isolated the zebrafish ortholog of Lyve1, and analyzed its expression pattern during embryogenesis, and under conditions where key regulators of lymphangiogenesis such as Prox1 and VegfC were depleted. Like humans, zebrafish embryos form lymph sacs, lymphangioblasts arise from venous endothelia, and they form asymmetric left and right collecting ducts. By monitoring the earliest lymphatic sprouting in the head, a pilot drug assay was performed showing rapamycin, an inhibitor of mammalian lymphangiogenesis, can also suppress zebrafish lymphangiogenesis. This work opens up a novel opportunity to further the understanding of, and potentially manipulate, human lymphangiogenesis.
肿瘤生长过程中诱导的淋巴管生成有助于转移。使用斑马鱼模型进行的遗传和化学筛选有可能增强我们对淋巴管生成的理解，并发现具有淋巴系统活性的药理制剂。在整个斑马鱼胚胎中进行大规模的淋巴管发育筛选需要特定的淋巴管内皮细胞标记物。我们分离了斑马鱼 Lyve1 的同源物，并分析了其在胚胎发生过程中的表达模式，以及在淋巴管生成的关键调节因子如 Prox1 和 VegfC 耗尽的情况下。与人类一样，斑马鱼胚胎形成囊淋巴管，淋巴管母细胞起源于静脉内皮细胞，它们形成不对称的左右收集管。通过监测头部最早的淋巴管发芽，进行了一项初步的药物检测，结果表明雷帕霉素，一种哺乳动物淋巴管生成抑制剂，也可以抑制斑马鱼的淋巴管生成。这项工作为进一步理解和潜在地操纵人类淋巴管生成开辟了新的机会。
