Human embryos that get too much or too little retinoic acid, a derivative of Vitamin A, can develop into babies with birth defects. New research at UC Irvine shows for the first time how embryonic cells may regulate levels of retinoic acid, giving scientists insight into how it acts as a signal between cells to control development of the brain, limbs and many other tissues in embryos.
Thomas Schilling, Richard White, Qing Nie and Arthur Lander of UCI studied the behavior of retinoic acid in zebrafish embryos, which often are used in genetic studies as models for human development because the transparent embryos are easy to examine and develop rapidly. The zebrafish genome also has been completely sequenced.
Retinoic acid is important to human health. In addition to its vital role in embryo development, it is used to treat patients with certain types of leukemia, and it is included in many acne medications because of its profound effects on skin cells. Vitamin A is found naturally in many foods, including liver, carrots, broccoli, kale and sweet potatoes.
“Vitamin A in the diet gets converted into retinoic acid, which scientists have known since the 1960s has amazing effects on cells and tissues,” said Schilling, associate professor of developmental and cell biology at UC Irvine. “If you don’t get enough Vitamin A in your diet – or if you get too much – your body compensates for that. Our study helps explain how this regulation occurs.”
This study appears Nov. 20 in the journal Public Library of Science Biology.
Within a certain range, cells can regulate levels of retinoic acid. Schilling and his colleagues found that if the level becomes too high, an enzyme called cyp26a1 degrades the excess and brings it back to normal. When levels drop too low, proteins called fibroblast growth factors, or FGFs, stop the retinoic acid from degrading as rapidly.
“Those two things work together to keep the whole system adjusted to the right level,” Schilling said. “Retinoic acid induces its own degradation, and FGFs, also present in the embryo, have the opposite effect by inhibiting retinoic acid degradation.”
Zebrafish embryos used in this study were genetically engineered to be unable to make enough retinoic acid. The UCI scientists implanted tiny retinoic acid-soaked beads, which gradually released retinoic acid into the embryos. Using genetically altered fish embryos in which cells become fluorescent in response to retinoic acid when illuminated with an ultraviolet light, the scientists tracked how the retinoic acid moved within the embryos. This study is among the first to examine the distribution of retinoic acid.
These data were analyzed in a mathematical model based on the different biological components of the embryo. This type of collaboration between biologists and mathematicians is key to understanding how signals work and act together in complex biological systems.
Previously, scientists focused on where retinoic acid is made within an embryo, “but now we’re hoping the results of our study will shift the focus of research to how the degradation of retinoic acid is controlled,” Schilling said. Hopefully this someday will help scientists better predict how retinoic acid behaves in the human body, leading to more effective drug treatments.
Jennifer Fitzenberger | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy