The zebrafish model has powerful advantages for studying embryonic development, said senior author Michael Tsang, Ph.D., assistant professor, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine.
"This gives us a better understanding of heart development during the embryonic stage and has implications for adult disease," he noted. "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."
Zebrafish are vertebrate animals whose transparent embryos develop rapidly, are small and easy to handle and, most importantly, grow outside of the mother. In earlier work, Dr. Tsang and his team bred a line of transgenic zebrafish with the gene for green fluorescent protein linked to a key signaling 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," Dr. Tsang said. "The embryos are like biosensors for FGF signaling, showing us what's happening in real time in living animals."
For the current paper, he and colleagues focused on a small molecule called BCI, which hyperactivated FGF signaling. They 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.
Knowing that, BCI could then be used as a tool to find out what effect Dusp6 inhibition would have on heart development. Zebrafish treated with BCI had a greater number of cardiac progenitor cells and, ultimately, larger hearts, Dr. Tsang said.
Unraveling the fibroblast growth factor pathway has broad implications for improving wound healing as well, Dr. Tsang said. For example, FGF2 has been used in treatment of chronic skin ulcers and following burn surgery in Japan. Thus, BCI alone or in combination with FGF2 might accelerate the healing process and improve wound repair.
Co-authors of the paper include the lead investigator Gabriela Molina, B.S., Wade Znosko, B.S., and Thomas Smithgall, Ph.D., Department of Microbiology and Molecular Genetics; Andreas Vogt, Ph.D., Pierre Queiroz de Oliveira, B.S., and John Lazo, Ph.D., Department of Pharmacology and Chemical Biology; Ahmet Bakan, B.S., Ivet Bahar, Ph.D., Weixiang Dai, Ph.D., and Billy Day, Ph.D., Department of Pharmaceutical Sciences. All authors are from the University of Pittsburgh.
The project was funded by grants from the National Institutes of Health and the Fiske Drug Discovery Fund.
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.
Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences
Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.
Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...
16.03.2018 | Event News
13.03.2018 | Event News
08.03.2018 | Event News
16.03.2018 | Earth Sciences
16.03.2018 | Physics and Astronomy
16.03.2018 | Life Sciences