What is it about?

Unlike humans, most fish do have two different kinds of blood vessels: "Normal" blood vessels (similar to those that humans have) and "secondary" blood vessels. The special feature of secondary blood vessels is the ability of the fish to regulate the flow of oxygen-carrying red blood cells into these secondary vessels. Secondary blood vessels are found mainly in the skin and the fins of the fish in very close contact with the surrounding water. Only when the fish need lots of oxygen (e.g. during fast swimming) and when the water is oxygen-rich, do red blood cells enter the secondary vessels in order to get additionally boosted with oxygen from the surrounding water. This is needed because fish gills - as magnificent as they are - have a hard time extracting enough oxygen from the water to support a high metabolism (that's likely the major reason why fish are not warm-blooded, and why specifically fast-swimming fish need to supplement the gill respiration with skin respiration vias this so-called secondary vascular system (SVS). In a recent study in Nature, Das et al. (2022) show that the secondary blood vessels of the anal and dorsal fin of zebrafish develop from lymphatics by transdifferentiation. This is amazing because it is the first time that such transdifferentiation from lymphatics into blood vessels has been seen in a physiological setting. In our opinion piece, we explicitly make the connection between the transdifferentiated blood vessels that Das et al. describe and the secondary vascular system. The interesting consequence of the transdifferentiation is the fact that the affected tissues are devoid of lymphatics. If all lymphatics transdifferentiated into SVS, fish might not have any "true" lymphatics. That is actually what some researchers believe. However, it seems that not all lymphatics transdifferentiate, but the exact extent and degree of the transdifferentiation are still unknown.

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Why is it important?

Nobody knows yet, how important this finding will become. It might remain an obscure developmental pathway limited to some fish species. Alternatively, we might discover similar developmental trajectories (i.e. vestigial mechanisms) in humans. In any case, it is clear that something like lymphatic-to-blood vessel transdifferentiation can happen in disease.


I have been interested in fish lymphatics since I was a Ph.D. student. It fascinated me that despite 200 years of research, the scientists had not come to an agreement on what the vascular system of fish looks like. Some claimed that they have a cardiovascular system and a lymphatic system just as we humans do, while others completely denied the existence of lymphatic vessels in fish. Now it looks as if fish have - apart from their primary cardiovascular system - a vascular system somewhere in between lymphatics and blood vessels.

Dr Michael Jeltsch
Helsingin Yliopisto

Read the Original

This page is a summary of: Lymphatic-to-blood vessel transdifferentiation in zebrafish, Nature Cardiovascular Research, May 2022, Springer Science + Business Media, DOI: 10.1038/s44161-022-00073-1.
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