New mechanism found for specialisation of lymphatic vessels

2021-05-03

The body’s lymphatic vessel system consists of specialised vessels whose function are critical for absorbing and transporting fluid. Taija Mäkinen’s group at IGP have identified a mechanism for how collecting lymphatic vessels are formed in mice, which could help to develop treatments for lymphatic diseases.

The lymphatic vessels form a network in the body which drains the tissues by absorbing fluid and transporting it back to the blood. There are two types of lymphatic vessels, the very thin lymphatic capillaries that absorb fluid in the tissues and the larger collecting vessels that contain valves that only allow the fluid to be transported in one direction.

If these functionally specialised vessel types are not established correctly it might lead to lymphatic diseases. As yet, the mechanism behind how the vessel types are formed has not been clarified but in the present study the researchers show that the gene regulatory protein FOXP2 is critical for the formation of functional collecting lymphatic vessels.

“We set out to identify genes that were active specifically in collecting lymphatic vessels in mice. One of the genes that we found was Foxp2, which encodes the protein FOXP2. This is a transcription factor, a protein that can control the activity of other genes, and the corresponding protein in humans has previously been implicated in the development of speech. In the vasculature, we could only detect FOXP2 in collecting lymphatic vessels and we hypothesised that it was involved in controlling the identity and function of these vessels,” says Taija Mäkinen.

In the next steps, the researchers discovered that during the formation of the collecting lymphatic vessels, FOXP2 was induced when a lymph flow is initiated. When they genetically removed the Foxp2 gene, so that no FOXP2 protein was produced, they found that the collecting lymphatic vessels were wider and had defective valves. Since FOXP2 is a transcription factor, they also found that it regulates the activity of some genes that were previously shown to be involved in lymphatic vessel and valve formation.

“Our results uncover a molecular mechanism for how functional valves are formed in collecting lymphatic vessels, which includes FOXP2 and is regulated by lymph flow. In humans there are genes and proteins that correspond to the ones we have found in mice and we think that modulation of FOXP2 could provide a therapeutic strategy to restore functional collecting lymphatic vessels,” says Taija Mäkinen.

The study was performed in collaboration with Swiss researcher and it has been published in EMBO Journal.

More information:
Paper in EMBO Journal
Taija Mäkinen’s research