Visualization of Lymphatic Vessel Development, Growth, and Function

Despite their important physiological and pathophysiological functions, lymphatic endothelial cells and lymphatic vessels remain less well studied compared to the blood vascular system. Lymphatic endothelium differentiates from venous blood vascular endot

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Visualization of Lymphatic Vessel Development, Growth, and Function Cathrin Pollmann, Rene´ Ha¨gerling, and Friedemann Kiefer

Abstract Despite their important physiological and pathophysiological functions, lymphatic endothelial cells and lymphatic vessels remain less well studied compared to the blood vascular system. Lymphatic endothelium differentiates from venous blood vascular endothelium after initial arteriovenous differentiation. Only recently by the use of light sheet microscopy, the precise mechanism of separation of the first lymphatic endothelial progenitors from the cardinal vein has been described as delamination followed by mesenchymal cell migration of lymphatic endothelial cells. Dorsolaterally of the embryonic cardinal vein, lymphatic endothelial cells reaggregate to form the first lumenized lymphatic vessels, the dorsal peripheral longitudinal vessel and the more ventrally positioned primordial thoracic duct. Despite this progress in our understanding of the first lymph vessel formation, intravital observation of lymphatic vessel behavior in the intact organism, during development and in the adult, is prerequisite to a precise understanding of this tissue. Transgenic models and two-photon microscopy, in combination with optical windows, have made live intravital imaging possible: however, new imaging modalities and novel approaches promise gentler, more physiological, and longer intravital imaging of lymphatic vessels.

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Introduction

Lymphatic vessels, the second branch of the mammalian vascular system, fulfill indispensible functions for tissue fluid homeostasis, trafficking of dendritic cells and macrophages as well as in dietary lipid resorption (Tammela and Alitalo 2010). Recently, the lymphatic vasculature has also been suggested to contribute to pathological processes, including tumor metastasis, inflammatory diseases, cardiac C. Pollmann • R. Ha¨gerling • F. Kiefer (*) Mammalian Cell Signaling Laboratory, MPI for Molecular Biomedicine, Ro¨ntgenstrasse 20, 48149 Mu¨nster, Germany 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_13, © Springer-Verlag Wien 2014

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hypertension, and obesity (Alitalo 2011). Despite these important physiological and pathophysiological functions, the lymphatic vessel system has traditionally been considered of “lesser significance” compared to blood vessels. Hence, elucidation of the molecular mechanisms controlling development, maturation, and function of lymphatic vessels for a long time lagged behind the research into blood vessel physiology and function. A trivial but nevertheless fundamental difference between blood and lymphatic vessels might underlie this lower interest, which is their relative invisibility. Lymphatic capillaries are only surrounded by a thin discontinuous basement membrane, covered by no or few mural cells and in the resting, largely collapsed state c