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Explained: A zebrafish gene that can promote heart regeneration

The fish is native to South Asia's Indo-Gangetic plains, where they are mostly found in the paddy fields and even in stagnant water and streams.

Written by Anuradha Mascarenhas , Edited by Explained Desk | Pune | Updated: December 1, 2020 1:10:43 pm
The ability of zebrafish to heal their heart after injury makes them an attractive model to investigate mechanisms governing the regenerative process.

Zebrafish – a tiny freshwater fish barely 2-3 cm long can efficiently regenerate its damaged heart within a short time period. Found in South Asia, it is a popular aquarium fish, frequently sold under the trade name Danio. Now, scientists at Pune-based Agharkar Research Institute have used this tiny animal model and identified genes that can promote heart regeneration. As reported in the high-impact Development journal, scientists have sought to decode the heart regeneration processes using this animal model.

Zebrafish, a suitable research model

Zebrafish is a small (2-3 cm long) freshwater fish found in the tropical and subtropical regions. The fish is native to South Asia’s Indo-Gangetic plains, where they are mostly found in the paddy fields and even in stagnant water and streams. The fish become adults at three months and survive 2-3 years in a laboratory condition. This fish’s unique characteristics lie in its transparency during its embryonic stages, allowing observing all organs, including beating heart and blood circulation.

A zebrafish attracts developmental biologists due to its adequate regeneration capacity of almost all its organs, including the brain, heart, eye, spinal cord. This makes it a suitable research model for biomedical scientists. Agharkar Research Institute has a state-of-art zebrafish housing where thousands of zebrafish are maintained (28 degrees Celsius water temperature with physiological water pH and conductance)are bred regularly. 📣 Follow Express Explained on Telegram

Ability to heal their heart

The ability of zebrafish to heal their heart after injury makes them an attractive model to investigate mechanisms governing the regenerative process. About two decades ago, Dr. Kenneth Poss, Professor at Duke University, USA, had first observed the zebrafish heart’s regenerative capacity. Dozens of labs worldwide are actively working to understand the mechanism behind the heart regeneration in zebrafish for the last two decades. Through years of research, scientists are coming closer to delineating the intricate pathways of zebrafish heart regeneration for further translational approaches.

Gene that promotes heart regeneration identified

Scientists used this tiny fish to identify genes/proteins that promote heart regeneration and its working model. Years of efforts have helped them identify the cellular communication network factor 2a (ccn2a), a gene that can promote heart regeneration by enhancing cardiomyocyte proliferation. “Ccn2a promotes the innate regenerative response of the adult zebrafish heart and maybe a promising therapeutic target for humans,” Dr Chinmoy Patra, Head of the Max-Planck Partner Group, Department of Developmental Biology, Agharkar Research Institute said. Earlier, ARI scientists Dr Patra, Debanjan Mukherjee and others had highlighted the importance of zebrafish to use as a model organism. Now they have identified the gene, which can promote heart regeneration. This gene enhances the proliferation of functional contractile heart cells called cardiomyocytes. They have also observed that this gene resolves the transient collagenous fibrotic scar resulting in faster regeneration. We want to investigate further the molecular pathways responsible for faster heart regeneration with the hope towards translational therapy, Dr Patra said

Promising therapeutic target for humans?

Cardiovascular diseases are the number 1 cause of deaths globally, taking an estimated 17.9 million lives each year, according to the World Health Organisation. Humans cannot regenerate their hearts like skin or liver. Humans cannot regenerate their hearts upon myocardial damage and a person who suffered a heart attack cannot functionally heal the damaged heart muscle, resulting in reduced pumping efficiency. While on the other hand, this unique fish has the full potential to regenerate its heart and restore its function after injury.

Till now, there is no treatment available to restore the damaged heart function in humans. Hence scientists have sought to decode the heart regeneration processes using this model animal, which can naturally regenerate their hearts efficiently so as to understand the processes which can illuminate strategies to improve human cardiac regeneration. The model is popular in industrial discovery. Dr. Reddy’s laboratory in Hyderabad already developed a zebrafish set up for research.

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