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FOXPY regulation of lymph flow

By Magda Hernández-Vásquez
28 June 2021

Confocal microscope image of a lymphatic valve, showing endothelial cell nuclei (blue) and extracellular matrix (magenta) on the leaflet of a valve in mouse mesenteric lymphatic vessel (green).

Micsroscope image showing a lymphatic valve in the mouse

Background

The lymphatic vascular system consists of a network of vessels that maintains fluid balance in the body and plays a vital role in immune responses. Lymphatic capillaries take up fluid, macromolecules and immune cells from the tissues. Once inside the vessels, the fluid, now called lymph, is transported along larger so called collecting lymphatic vessels to lymph nodes and further to blood circulation. Efficient unidirectional flow of lymph relies on luminal valves present in the collecting vessels. Malfunction of the lymphatic system, for instance due to defective valves, can lead to tissue swelling called lymphedema.

How are the functional differences between fluid absorbing lymphatic capillaries and fluid transporting collecting vessels established? To answer this question, we identified genes that are differentially expressed between endothelial cells lining different types of blood and lymphatic vessels in the mouse skin. We identified Foxp2, a Forkhead transcription factor that regulates the development of language and speech in human, as a gene that was specifically expressed in collecting lymphatic vessels. FOXP2 expression was controlled by fluid flow downstream of the major flow-responsive transcription factor Foxc2 that is a known regulator of collecting lymphatic vessel formation. Mice lacking Foxp2 had enlarged collecting vessels and defective valves, which was associated with reduced expression of known valve-regulators such as the NFATc1 transcription factor.

Our findings identify FOXP2 as a new critical regulator of collecting vessel morphogenesis, and highlight the existence of unique transcription factor codes for the establishment of endothelial cell identities in functionally specialized vessels. Restoration of functional collecting lymphatic vessel network is important for effective treatment of lymphedema, however specific therapeutic approaches promoting collecting vessel formation are lacking. Identification of transcriptional regulators of collecting vessel identity such as FOXP2 may provide a rationale for the development of such approaches.

Further reading

https://www.embopress.org/doi/full/10.15252/embj.2020107192

About the author:

Dr. Magda Hernández-Vásquez is a postdoc in Taija Mäkinen’s lab at IGP. She studies the role and regulation of collecting lymphatic vessels by functionally characterizing novel genes that are selectively expressed in these vessels.

Photo of Magda Hernández-Vásquez Dr. Magda Hernández-Vásquez
Uppsala University
Dept. Immunology, Genetics and Pathology
Rudbeck Laboratory C11
Dag Hammarskjölds Väg 20
751 85 Uppsala
Sweden


magda.hernandez@igp.uu.se
www.igp.uu.se/research/vascular-biology/taija-makinen/

www.makinenlab.com/
linkedin.com/in/magda-nohemí-hernández-vásquez-2b7499130

Last modified: 2021-06-28