Zebrafish Model Reveals Molecule that Determines Heart Size

Experts at the University of Pittsburgh report an amazing discovery, which could lead to many potential applications in the field of medicine. Using zebrafish as model animals, they managed to accurately pinpoint an enzyme inhibitor that allows for a large increase in the number of progenitor cells inside the developing heart, essentially increasing its size considerably. Details of the achievement will be published in the advanced online issue of the journal Nature Chemical Biology.

Zebrafish were selected for the new investigation because of the similarities they have to our own. “This gives us a better understanding of heart development during the embryonic stage and has implications for adult disease. 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,” explains the importance of the find UP School of Medicine Department of Microbiology and Molecular Genetics assistant professor Michael Tsang, PhD, who is also the senior author of the paper.

 

Another reason why the study succeeded is the fact that zebrafish embryos develop outside their mothers, and also that they grow rapidly, and are transparent. In a line of artificially-mutated embryos, which were modified to express the gene for green fluorescent protein associated with a key signaling pathway of fibroblast growth factors (FGF), the experts observed the actions of some important factors involved with the embryonic development process.

 

“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,” Tsang reveals. The team notes that FGF signaling inside the model animals was hyperactivated by a small molecule called BCI, and this happened because BCI inhibited the action of the feedback regulator Dusp6, an enzyme that usually plays a role in reducing the FGF signal in the average embryo.

 

By manipulating the levels of BCI, the researchers were able to obtain less FGF inhibition, which eventually led to the resulting embryos having larger hearts. Now, the experts are working on devising a way to translate the find into humans, and assessing the potential therapeutic use for the molecule.