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 lym
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Development of Secondary Lymphoid Organs in Relation to Lymphatic Vasculature Serge A. van de Pavert and Reina E. Mebius
Abstract 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.
7.1
Introduction
Lymphatic vessels are instrumental for the transport of exudates, which develop at capillary beds, back to the bloodstream. This fluid collects as lymph in lymphatic vessels and moves to the draining lymph nodes. Cells and small molecules derived from these peripheral sites are carried with the lymph to the draining lymph nodes. S.A. van de Pavert Royal Netherlands Academy of Arts and Sciences, Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands e-mail: [email protected] R.E. Mebius (*) Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081BT Amsterdam, The Netherlands e-mail: [email protected] F. Kiefer and S. Schulte-Merker (eds.), Developmental Aspects of the Lymphatic Vascular System, Advances in Anatomy, Embryology and Cell Biology 214, DOI 10.1007/978-3-7091-1646-3_7, © Springer-Verlag Wien 2014
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S.A. van de Pavert and R.E. Mebius
In the absence of an infection this does not lead to measurable changes within these lymph nodes. However, upon infection, antigen-presenting cells will carry antigen derived from the infected area and travel with the lymph to the draining lymph nodes. Here they will present the antigen to lymphocytes, which will start the adaptive immune response. Hence, properly placed lymphatic vessels and lymph nodes are crucial for an adequate and fast immune response needed for protection against infectious agents that enter our body. It is therefore not surprising that both lymphatic vessels and lymph nodes are formed in a coordinated fashion, as lymphatic vessels and lymph nodes form within the same time frame, while sharing essential differentiation signals. Here, we will discuss this coordinated process leading to the formation of a functional lymphatic system.
7.2
Lymph Node Formation
Lymph n
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