Development of the mammalian lymphatic vasculature is a stepwise process requiring the specification of lymphatic endothelial cell progenitors in the embryonic veins, and their subsequent budding to give rise to most of the mature lymphatic vasculature. In mice, formation of the lymphatic vascular network starts inside the cardinal vein at around E9.5 when a subpopulation of venous endothelial cells get committed into the lymphatic lineage by their acquisition of Prox1 expression. Here we will continue with our long-time efforts to accomplish a detailed cellular and molecular characterization of the genes and mechanisms regulating the early steps leading to the formation of the mammalian lymphatic vasculature. A better understanding of basic aspects of early lymphatic development and the availability of novel tools and animal models has been instrumental in the identification of important novel functional roles of the lymphatic vasculature.

Public Health Relevance

Here we propose to identify and characterize new candidate genes participating in early stages of lymphatic development, provide novel clues about the role of energy and mitochondria in LEC specification and differentiation, and characterize the processes of lymphatic tube and lumen formation. This knowledge will help us gain a better understanding of most key aspects regulating developmental lymphangiogenesis and provide additional clues on genes and mechanisms responsible for functional defects leading to lymphatic malfunction. This knowledge will facilitate the treatment of pathological conditions such as inflammation, autoimmunity, cancer, metabolic disorders, and maybe even neurological diseases that could all be consequence of a defective or somehow impaired lymphatic vasculature.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Galis, Zorina S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
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
Liu, Xiaolei; Gu, Xiaowu; Ma, Wanshu et al. (2018) Rasip1 controls lymphatic vessel lumen maintenance by regulating endothelial cell junctions. Development 145:
Louveau, Antoine; Herz, Jasmin; Alme, Maria Nordheim et al. (2018) CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci 21:1380-1391
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

Showing the most recent 10 out of 27 publications