Characterization of lymphatic development in the Central Nervous System

Authors

• RM Izen
• U Yutaka
• Y Mukoyama

Abstract

Traditionally, the Central Nervous System (CNS) has been viewed as an immune-privileged environment with no lymphatic vessels. This view was overturned by recent studies finding lymphatic vessels in the dural membrane surrounding the brain. The unique distribution of the brain lymphatic vessels poses fundamental questions in the field of lymphatic vessel development: How does the CNS lymphatic vasculature develop on the surface of, but not within, the brain? What is the developmental origin of these dural lymphatic vessels? We have developed whole-mount imaging of lymphatic vasculature in embryonic brain. Visualization of CNS lymphatic vasculature has been done by Prox1-promoter directed GFP reporter mice. We have successfully visualized Prox1-GFP+ vessels on the surface of the brain at E14.5, prior to the coverage of lymphatic vessels in the head skin. This result suggests that the dural lymphatic development can be independent from the skin lymphangiogenesis. We are currently carrying out an extensive whole-mount imaging analysis to examine whether dural lymphatics can be derived from neighboring veins on the surface of the brain. Ultimately, these studies will provide insights into tissue-specific lymphangiogenesis that is adapted to the complex tissue structure and function of the CNS.

Scientific Focus Area: Developmental Biology

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