A group of researchers say they have clarified the role that retinoic acid plays in limb development. Their study in Current Biology says that retinoic acid controls the development (or budding) of forelimbs, but not hindlimbs, and that retinoic acid is not responsible for patterning (or differentiation of the parts) of limbs. This research corrects longstanding misconceptions about limb development and provides new insights into congenital limb defects. Gregg Duester, Ph.D., professor of developmental biology at Burnham Institute for Medical Research (Burnham), along with Xianling Zhao, Ph.D., and colleagues, did studies of mice and zebrafish and found that retinoic acid suppresses the gene fibroblast growth factor 8 (Fgf8) during the period when forelimb budding occurs, creating a suitable environment for the creation of forelimb buds. “For decades, it was thought that retinoic acid controlled limb patterning, such as defining the thumb as being different from the little finger,” said Duester. “However, we have demonstrated in mice that retinoic acid is not required for limb patterning, but rather is necessary to initiate the limb budding process. We also found that retinoic acid was unnecessary for hindlimb (leg) budding, but was needed for forelimb (arm) budding.” Congenital birth defects of the arms, legs, hands or feet result from improper development of limb bud tissues during embryogenesis. These processes are regulated by signaling molecules that control the growth and differentiation of progenitor cells by regulating specific genes. One of these signaling molecules is retinoic acid, a metabolite produced from vitamin A (retinol), which plays a key role in the development of limbs and other organs. Duester's lab was instrumental in identifying Raldh2 and Raldh3, the genes responsible for retinoic acid synthesis, and has shown that retinoic acid is only produced by certain cells at precise stages of development. In the study, the team of scientists showed that mice missing the Raldh2 and Raldh3 genes, which normally die early and do not develop limbs, could be rescued by treatment with a small dose of retinoic acid. However, forelimb development was stunted, suggesting that retinoic acid is required for forelimb but not hindlimb development. In zebrafish, the forelimb (pectoral fin) is also missing in retinoic acid-deficient embryos, but they were able to rescue fin development by treating such embryos with a drug that reduces fibroblast growth factor activity, thus supporting the hypothesis that retinoic acid normally reduces this activity. By providing a more complete understanding of the molecular mechanisms involved in normal limb development, these findings may lead to new therapeutic or preventative measures to combat congenital limb defects, such as Holt-Oram syndrome, a birth defect characterized by upper limb and heart defects.
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- Fibromyalgia Is Not All In The Head, It's In Skin, Paper Concludes
- Two 'Facts' in Modern Physics Courses that everyone learns but just ain't so...
- The Elusive H7N9 Virus: Chinese Researchers Predict Future Pandemic
- The Plot Of The Week - B Production Cross Section
- Finally, Immunotherapy for Cancer Comes to Life
- Pregnancy: Moderate Drinking Doesn't Harm Baby's Neurodevelopment
- New York City School Goes Vegetarian - CNN Gushes How Enthusiastic Students Are Over 'Healthy Choices'
- "Fox is only a problem for Democrats because they think it is a problem - the New York Times has..."
- "I googled him to make sure he was real - he is a full-on loon. I doubt I would disagree about the..."
- "Yeah, that was unfortunate. I'm not sure who he is, but I rarely see anything as negative even..."
- "One does suspect that US Democrats and British Guardianistas do tend to look on Fox News viewers..."
- "Good advise ;)..."
- Less is more: Novel cellulose structure requires fewer enzymes to process biomass to fuel
- A battery made of wood?
- Group-based child care is linked to reduced emotional problems in children of depressed mothers
- Unexpected behavior of well-known catalysts
- Long-term study reports deep brain stimulation effective for most common hereditary dystonia