Küchler Axel M, Gjini Evisa, Peterson-Maduro Josi, Cancilla Belinda, Wolburg Hartwig, Schulte-Merker Stefan
Exelixis, Inc., 170 Harbor Way, South San Francisco, California 94083, USA.
Curr Biol. 2006 Jun 20;16(12):1244-8. doi: 10.1016/j.cub.2006.05.026.
Lymphangiogenesis results in the formation of a vascular network distinct from arteries and veins that serves to drain interstitial fluid from surrounding tissues and plays a pivotal role in the immune defense of vertebrates as well as in the progression of cancer and other diseases . In mammals, lymph vessels are lined by endothelial cells possibly sprouting from embryonic veins, and their development appears to be critically dependent on the function of PROX1 and VEGFC signaling . The existence of a lymphatic system in teleosts has been a matter of debate for decades. Here we show on the morphological, molecular, and functional levels that zebrafish embryos develop a lymphatic vasculature that serves to retrieve components of the interstitium to the lymph system. We demonstrate the existence of vessels that are molecularly and functionally distinct from blood vessels and show that the development of these vessels depends on Vegfc and VEGFR-3/Flt4 signaling. These findings imply that the molecular components controlling lymphangiogenesis in zebrafish and mammals are conserved and that the zebrafish lymphatic system develops early enough to allow in vivo observations, lineage tracing, and genetic as well as pharmacological screens.
淋巴管生成导致形成一个与动脉和静脉不同的血管网络，该网络用于从周围组织引流间质液，并在脊椎动物的免疫防御以及癌症和其他疾病的进展中起关键作用。在哺乳动物中，淋巴管由可能从胚胎静脉中萌发的内皮细胞排列而成，其发育似乎严重依赖于PROX1和VEGFC信号传导的功能。几十年来，硬骨鱼中淋巴系统的存在一直是一个有争议的问题。在这里，我们在形态、分子和功能水平上表明，斑马鱼胚胎发育出一个淋巴管系统，该系统用于将间质成分回收到淋巴系统。我们证明了存在在分子和功能上与血管不同的血管，并表明这些血管的发育依赖于Vegfc和VEGFR-3/Flt4信号传导。这些发现意味着控制斑马鱼和哺乳动物淋巴管生成的分子成分是保守的，并且斑马鱼淋巴系统发育得足够早，以便进行体内观察、谱系追踪以及基因和药理学筛选。
