Periodic Reporting for period 4 - CAVEHEART (Heart regeneration in the Mexican cavefish: The difference between healing and scarring)
Periodo di rendicontazione: 2021-09-01 al 2022-08-31
Complete regeneration of the adult heart after injury is a feature exclusive to a limited number of species, including lower vertebrates such as the zebrafish and salamander. Injury to a zebrafish heart results in a spectacular scar-free regeneration process, with the wound tissue completely being replaced with new, functional cardiac muscle. If we can discover what fundamental mechanisms drive natural heart regeneration in fish, we can directly apply this knowledge to heal the human heart after a heart attack and during heart failure. Differences in inflammation and scarring are thought to be important differences between animals that can regenerate their hearts and animals that cannot, but not much is known about how these processes regulate heart regeneration.
In this project we use Astyanax mexicanus, the Mexican cavefish, as well as zebrafish, to study the mechanisms underlying scarring and inflammation during heart regeneration. Astyanax mexicanus is a single fish species comprising cave-dwelling and surface populations. These two populations arose around 10.000 - 8 million years ago when flooding caused surface fish living in rivers in Northern Mexico to enter the caves. River levels retreated over time and many caves never reconnected to the river and the fish evolved into different cavefish populations, whilst remaining the same species capable of interbreeding with their surface fish counterparts. During their independent evolution in the caves, the fish lost their eyes and pigment, redundant in the absence of light. Instead, they developed other features that helped survive in a cave. We found that, like zebrafish, the river surface fish regenerate their heart, while, cavefish cannot and form a permanent fibrotic scar, similar to the human injury response.
Comparing heart regeneration versus scarring in the same species allows us to focus directly on the mechanisms underlying this difference.
The results on the QTL data are slightly delayed as a result of the pandemic, but will have our full focus in the next months to also finalise this data and disseminate.
The project has also provided us with many new findings of interest that will be the focus of new grant applications.