Under normal conditions, the lymphatic network maintains fluid homeostasis by draining lymph fluid from extracellular spaces, absorbs lipids from the intestinal tract, and transports white blood cells and antigen- presenting cells to lymphoid organs. During infection, the lymphatic vasculature is the main route for the immune response, and in cancer, tumor cells migrate via the lymphatic vasculature to lymph nodes and distant organs. Malfunctions of the lymphatic system can lead to congenital or inherited disorders such as lymphedema, a disfiguring and disabling disorder that is caused by imbalance in lymph absorption and often characterized by swelling of the extremities. A better knowledge of the cellular and molecular features controlling normal lymphatic vasculature development should facilitate our understanding of pathologic lymphatic conditions that lead to inflammation, autoimmunity, cancer, and obesity and to improve the clinical treatment of primary and secondary forms of lymphedema.

Public Health Relevance

Our understanding of the genes and mechanisms controlling the formation of the lymphatic vasculature has improved greatly during the last decade thanks to the availability of molecular markers and animal models with various degrees of lymphatic defects. This knowledge has helped us not only to improve our understanding of lymphatics-related pathologic conditions but also to re-evaluate the functional roles of the lymphatic vasculature in health and disease. Therefore, increasing our understanding of developmental lymphangiogenesis should keep impacting on our understanding of pathologic lymphatic conditions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL073402-10
Application #
8368141
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Tolunay, Eser
Project Start
2003-05-01
Project End
2017-06-30
Budget Start
2012-07-16
Budget End
2013-06-30
Support Year
10
Fiscal Year
2012
Total Cost
$437,500
Indirect Cost
$187,500
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
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Louveau, Antoine; Filiano, Anthony J; Kipnis, Jonathan (2018) Meningeal whole mount preparation and characterization of neural cells by flow cytometry. Curr Protoc Immunol 121:
Gil, Hyea Jin; Ma, Wanshu; Oliver, Guillermo (2018) A novel podoplanin-GFPCre mouse strain for gene deletion in lymphatic endothelial cells. Genesis 56:e23102
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Ma, Wanshu; Oliver, Guillermo (2017) Lymphatic Endothelial Cell Plasticity in Development and Disease. Physiology (Bethesda) 32:444-452
Escobedo, Noelia; Oliver, Guillermo (2017) The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity. Cell Metab 26:598-609
Escobedo, Noelia; Proulx, Steven T; Karaman, Sinem et al. (2016) Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice. JCI Insight 1:
Yang, Ying; Oliver, Guillermo (2014) Development of the mammalian lymphatic vasculature. J Clin Invest 124:888-97
Yang, Ying; Oliver, Guillermo (2014) Transcriptional control of lymphatic endothelial cell type specification. Adv Anat Embryol Cell Biol 214:5-22
Srinivasan, R Sathish; Escobedo, Noelia; Yang, Ying et al. (2014) The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors. Genes Dev 28:2175-87

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