Lymphatic Development

Embryologically, lymphatics are derived from endothelial progenitors that also give rise to venous endothelium under the influence of several growth factors, and their receptors that are differentially expressed during development. Lymphatic develop as off-"buds" derived from the venous system and was originally described in the classical studies by Florence Sabin. The first step in progenitor commitment to lymphatic phenotype is induction of the lymphatic specific transcription factor, Prox-1, followed by the release of secondary lymphoid chemokines (SLCs). LECs expressing these markers may further increase VEGF-R3 expression [10], which increases their sensitivity to VEGF-C/D and helps maintain their commitment to the LEC lineage.

This second step in lymphatic development appears to require signaling through the receptor tyrosine kinase Syk and its substrate, SLP-76 [11]. Signals from the Syk/SLP-76 system appear to be crucial for maintaining the separation of the blood and lymphatic systems, since deletion of either gene leads to anastomosis of blood and lymphatic vessels. It is interesting that while Syk/SLP-76 are certainly determinants of lymphatic development, it is not clear that they are proteins that are expressed by endothelium. It has therefore been suggested that Syk/SLP-76 could (1) activate lymphoid progenitor cells (which lose Syk/SLP-76 during maturation), (2) modulate the release of IL-2, or (3) be related to platelet degranulation, which is affected by Syk/SLP-76 [12].

In the adult, venous endothelial cells in lymphatic buds express VEGF-R3, which in endothelium is generally specific for lymphatic endothelial cells, indicating that some venous endothelial cells retain an intermediate phenotype, at

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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