European Commission logo
English English
CORDIS - EU research results
CORDIS

Navigating lymphatic formation and function in health and disease

Project description

Lymphatic vessel characterisation in healthy and diseased states

The goal of the EU-funded LymphMap project is to uncover the regulators of the formation and functionality of lymphatic vessels in health and disease. The project capitalises on the team's previous studies on zebrafish that revealed the cellular and molecular events in the development of the lymphatic system. These studies unveiled the origins, specification and mechanisms of the formation of lymphatic endothelial cells (LECs) in the developing embryo. The current research programme will characterise in-depth the cellular origin and molecular signature of LECs as well as the formation of organ-specific lymphatics and lymphatic vessels during regeneration and disease. The focus of the current research is on in vivo dynamics and cross-organ comparative analysis to provide knowledge on lymphatic diversity in health and disease.

Objective

For many years, lymphatic vessels have been viewed as inert fluid conduits whose open structure allows for passive flow of antigens, proteins and cells from peripheral tissues to lymphoid organs. Yet, recent discoveries highlighting novel functions and heterogeneous origins of the lymphatic endothelium, call for reevaluation of the passive lymphatic-vessel paradigm. During the past decade, we have used the zebrafish (ZF) to detail the cellular and molecular events underlying the development of the lymphatic system. Our discoveries have greatly contributed to our understanding of the origins, specification and mechanisms of formation of lymphatic endothelial cells (LECs) in the developing embryo. In line with our past achievements, we now aim towards novel directions- to transform the adult ZF into an equally convenient model for the study of lymphatic diversity. The overall goal of LymphMap is to reveal the multiple regulatory levels that coordinate the formation and functionality of lymphatic vessels in health and disease. To this end, we will carry out a comprehensive research program characterizing four distinct aspects of lymphatic biology:
1.Cellular origins and molecular signature of LECs
2.Formation and specialization of organotypic lymphatics
3.Lymphatic vessels during organ regeneration
4.Lymphatic involvement in human disease
Our experimental strategy involves the combination of high-resolution imaging, global expression profiling and regeneration models in adult ZF, with analyses of human-derived LECs in various clinical settings. The important and unique aspects of our approach are the focus on in vivo dynamics, and the cross-organ comparative analysis, which will likely provide the much-needed knowledge on lymphatic diversity in health and disease. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving lymphatics as passive bystanders, but rather as orchestrators of tissue morphogenesis and regeneration.

Host institution

WEIZMANN INSTITUTE OF SCIENCE
Net EU contribution
€ 2 000 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

See on map

Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 2 000 000,00

Beneficiaries (1)