Large multicellular organisms with a high metabolic demand use carrier molecules to distribute oxygen within their bodies. In vertebrates a closed vascular system guides the transport of these carrier molecules. Therefore the vascular system has to be functional early in development. When the human embryo reaches the size of approximately 3 mm at embryonic day 22, its heart starts beating. Later, when the cardiovascular system is already functioning, a second vascular system develops: the lymphatic system. Unlike the cardiovascular system it is not a circulatory system. Lymphatic flow starts in blind-ended capillary networks that penetrate most of the body tissues. Collecting lymphatics drain the capillary networks and after collecting fluid from many tributaries the largest collecting lymphatic vessel (the thoracic duct) ultimately reaches the veins. A schematic view of the general setup of the lymphatic system is given in Figure 1.
Compared to our tremendous knowledge about the cardiovascular system the understanding of the lymphatic system is still very rudimentary. The lymphatic system has lagged behind the cardiovascular system both in its discovery and exploration, probably due to the cardiovascular system's visual prevalence and importance.
Retrospectively, three heydays have shaped our understanding of the lymphatic system. The first took place during the first years of the 20th century when researchers like Sabin, Kampmeier, Huntington and McClure were studying the ontogeny of the lymphatic system (reviewed by Wilting et al. 1999). The second boost of knowledge resulted from the use of the electron microscope during the 1960s to solve questions about the fine structure of the initial lymphatics and their functioning (reviewed by Leak 1970). At the moment, lymphatic research is experiencing an impressive comeback thanks to the arrival of molecular biology, genetics and, last but not least, by the discovery of markers specific for lymphatic endothelium (reviewed by Oliver and Detmar 2002).