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Zebrafish model helps scientists identify molecule that regulates heart size

London, July 6 (ANI): University of Pittsburgh researchers say that their experiments on zebrafish have identified an enzyme inhibitor that enables the creature to increase the number of cardiac progenitor cells, and thus influences the size of the developing heart.

Dr. Michael Tsang, an assistant professor in the Department of Microbiology and Molecular Genetics at the university’s School of Medicine, strongly believes that the zebrafish model has powerful advantages for studying embryonic development.

“This gives us a better understanding of heart development during the embryonic stage and has implications for adult disease,” Nature magazine quoted him as saying.

“As we try to create treatments that restore normal function to damaged or diseased tissues, it will help us to know the biologic pathways and signals that formed these organs whole and healthy in the first place. This information can be gained by studying developmental biology,” he added.

His team previously bred a line of transgenic zebrafish with the gene for green fluorescent protein linked to a key signalling pathway of fibroblast growth factors (FGFs), a family of proteins that are essential in embryonic development.

“The transgenic zebrafish embryos allow us to actually see when a drug or compound influences FGFs because the cells glow green. The embryos are like biosensors for FGF signaling, showing us what’s happening in real time in living animals,” Dr. Tsang said.

During the current study, the researchers focused on a small molecule called BCI, which hyperactivated FGF signalling.

Dr. Tsang and his colleagues then figured out how BCI blocked the activity of an enzyme called Dusp6, a feedback regulator that would otherwise have tamped down the enhanced FGF signal.

The researchers said that knowing that could enable BCI to be used as a tool to find out what effect Dusp6 inhibition would have on heart development.

According to them, zebrafish treated with BCI had a greater number of cardiac progenitor cells and, ultimately, larger hearts.

Dr. Tsang said that unravelling the fibroblast growth factor pathway could have broad implications for improving wound healing as well.

Given that FGF2 has been used in treatment of chronic skin ulcers and following burn surgery in Japan, he says, BCI alone or in combination with FGF2 might accelerate the healing process and improve wound repair.

A research article on this work has been published in the journal Nature Chemical Biology. (ANI)

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