Transcriptional Control of Lymphatic Endothelial Cell Type Specification
The lymphatic vasculature is the “sewer system” of our body as it plays an important role in transporting tissue fluids and extravasated plasma proteins back to the blood circulation and absorbs lipids from the intestinal tract. Malfunction of the lymphat
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Transcriptional Control of Lymphatic Endothelial Cell Type Specification Ying Yang and Guillermo Oliver
Abstract The lymphatic vasculature is the “sewer system” of our body as it plays an important role in transporting tissue fluids and extravasated plasma proteins back to the blood circulation and absorbs lipids from the intestinal tract. Malfunction of the lymphatic vasculature can result in lymphedema and obesity. The lymphatic system is also important for the immune response and is one of the main routes for the spreading of metastatic tumor cells. The development of the mammalian lymphatic vasculature is a stepwise process that requires the specification of lymphatic endothelial cell (LEC) progenitors in the embryonic veins, and the subsequent budding of those LEC progenitors from the embryonic veins to give rise to the primitive lymph sacs from which the entire lymphatic vasculature will eventually be derived. This process was first proposed by Florence Sabin over a century ago and was recently confirmed by several studies using lineage tracing and gene manipulation. Over the last decade, significant advances have been made in understanding the transcriptional control of lymphatic endothelial cell type differentiation. Here we summarize our current knowledge about the key transcription factors that are necessary to regulate several aspects of lymphatic endothelial specification and differentiation.
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Overview of the Stepwise Process Leading to the Formation of the Lymphatic Network
Mammals have two interdependent circulatory systems—the blood vasculature and the lymphatic vasculature. Although detailed descriptions of the blood vascular system were available as early as the sixth century BC, those of the lymphatic vasculature were in the seventeenth century AD by Asellius. In contrast to the Y. Yang • G. Oliver (*) Department of Genetics, St. Jude Children’s Research Hospital, Memphis, TN, USA 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_2, © Springer-Verlag Wien 2014
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Y. Yang and G. Oliver
function of the blood vasculature in transporting blood throughout the body, the lymphatic vasculature is essential for maintaining interstitial fluid homeostasis. The main physiological functions of the lymphatic vasculature include draining and returning fluid from the extracellular tissue spaces back to the blood circulation, absorbing lipids from the intestinal tract and tissues, and transporting immune cells to lymphoid organs. During the formation of the blood vascular network, the Notch signaling pathway is required to promote arterial cell fate differentiation (De Val and Black 2009; Kokubo et al. 2005; Lawson et al. 2001). On the other hand, the orphan nuclear receptor COUP-TFII promotes venous fate differentiation by inhibiting Notch signaling and other arterial specification genes (You et al. 2005). Studies on the lymphatic networ
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