Development of secondary lymphoid organs in relation to lymphatic vasculature.

Although the initial event in lymphatic endothelial specification occurs slightly before the initiation of lymph node formation in mice, the development of lymphatic vessels and lymph nodes occurs within the same embryonic time frame. Specification of lymphatic endothelial cells starts around embryonic day 10 (E10), followed by endothelial cell budding and formation of the first lymphatic structures. Through lymphatic endothelial cell sprouting these lymph sacs give rise to the lymphatic vasculature which is complete by E15.5 in mice. It is within this time frame that lymph node formation is initiated and the first structure is secured in place. As lymphatic vessels are crucially involved in the functionality of the lymph nodes, the recent insight that both structures depend on common developmental signals for their initiation provides a molecular mechanism for their coordinated formation. Here, we will describe the common developmental signals needed to properly start the formation of lymphatic vessels and lymph nodes and their interdependence in adult life.