The human heart cannot regenerate new muscle when damaged but its vertebrate cousin the zebrafish, or Danio rerio, has the ability to regenerate almost all its organs including the heart, the spinal cord, the liver, the pancreas and the kidneys. This has made it the subject of research at 15 laboratories in India as scientists explore and seek to extrapolate its cell behaviour to higher organisms.
The tiny freshwater fish, native to the southeastern Himalayan region, is found in streams, lakes, ponds and rice field marshes. It develops in the water from the zygote stage itself, making it ideal for research.
“The embryo develops outside the mother’s body, and since they are transparent they can be monitored under the microscope,” said Rakesh Mishra, director of Centre for Cellular and Molecular Biology, Hyderabad. The transparency makes embryos amenable to gene manipulation techniques. The zebrafish can provide up to 200 embryos in one go, and are ready to breed again in days..
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CCMB is studying the function of Hox genes that help shape the body’s axis while the embryo is formed. “Since most body parts show regeneration capacity, we are trying to look at the function of these genes in the regenerated parts also,” Mishra said.
At Mumbai’s Tata Institute of Fundamental Research, researchers have used the zebrafish as a model to study microvillus inclusion disease that affects children, often leading to death. The TIFR findings, reported online in Mechanisms of Development, will appear in print next month.
And at Pune’s Agharkar Research Institute, which set up a zebrafish facility two years ago, researchers have set about identifying the molecules that help the heart regenerate. “We are screening five molecules,” said Dr Chinmoy Patra of the Developmental Biology group, who did his doctoral thesis at Max Planck Institute for Heart and Lung Research. He said preliminary data showed that a couple of these molecules are plausibly responsible for regeneration.
Dr Surendra Ghaskadbi, senior scientist in ARI’s developmental biology group, said the project on heart regeneration in zebrafish is the first of its kind in India. “It is well known that complex organisms such as human beings, which evolved relatively recently, have lost their capacity to regenerate most organs,” he said. “If the secrets of heart regeneration in zebrafish are learnt, one can think of applying them to humans.”
Around 50 million people in India are estimated to be suffering from coronary heart diseases.
TIFR’s research has linked microvillus inclusion disease to mutations in a gene called myosin Vb, also expressed in the intestinal epithelium of zebrafish. Dr Mahendra Sonawane and colleagues Jaydeep Sidhaye, Clyde Pinto, Shweta Dharap, Tressa Jacob and Shobha Bhargava found that mutations in this gene leads to defects in development of the epidermis. They then researched why mutant fishes were dying at later times although the epidermis restores its normal architecture. To their surprise, they found intestinal defects in zebrafish were almost identical to those in humans.
“One can now screen for potential drugs to treat the disease… enough mutants could be obtained for such a screen,” Sonawane said.