Study shows how embryos regulate vitamin A derivatives

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.

Source: University of California - Irvine

Related stories:

Regulation of the retinoic acid gradient in zebrafish embryos
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 published this week in the open-access journal PLoS Biology shows for the first time how embryonic cells may regulate levels of retinoic acid, providing insight into how retinoic acid signaling interacts with other key developmental signals to control development of the brain, limbs, and many other tissues in embryos.
Determining the structure of nuclear receptor has implications for a host of diseases
In a study published this week in PLoS Biology, Eric Xu and colleagues have determined the molecular structure of a nuclear receptor, which regulates the expression of specific genes within cells, that may serve as a drug target for diseases related to heart and blood vessel development, human embryonic development and female infertility. Researchers also found that the receptor, named COUP-TFII, is activated by retinoic acid, a form of Vitamin A.
New stem cell tools to aid drug development
SCIENTISTS have designed, developed and tested new molecular tools for stem cell research to direct the formation of certain tissue types for use in drug development programmes.
New insights into the regulation of PTEN tumor suppression function
The PTEN tumor suppressor gene controls numerous biological processes including cell proliferation, cell growth and death. But PTEN is frequently lost or mutated; in fact, alteration of the gene is so common among various types of human cancer that PTEN has become one of the most frequently mutated of all tumor suppressors.
Good news for a fast-wrinkling generation: Some anti-aging methods work
Fine wrinkles, deeper creases, saggy areas around the mouth and neck – the sights in the mirror that make baby boomers wince – are not inevitable. They result from a structural breakdown inside the skin that some existing treatments effectively counteract by stimulating the growth of new, youthful collagen, University of Michigan scientists say.
Many paths, few destinations: How stem cells decide what they'll be
How does a stem cell decide what specialized identity to adopt – or simply to remain a stem cell? A new study suggests that the conventional view, which assumes that cells are “instructed” to progress along prescribed signaling pathways, is too simplistic. Instead, it supports the idea that cells differentiate through the collective behavior of multiple genes in a network that ultimately leads to just a few endpoints – just as a marble on a hilltop can travel a nearly infinite number of downward paths, only to arrive in the same valley.
First do no harm? UH prof taking opposite approach to treat asthma
One month of tough breathing may help asthma sufferers breathe easier in the long run, according to research from one University of Houston professor.
Method to deliver molecules within embryonic stem cells improves differentiation
Embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. However, the inability of stem cells to efficiently develop into the desired specific cell type – such as muscle, skin, blood vessels, bone or neurons – now limits the potential clinical utility of this therapy.

News discussion:

Medicine & Health news