Embryology study offers clues to birth defects (w/Video)

June 9, 2009

Gregg Duester, Ph.D., professor of developmental biology at Burnham Institute for Medical Research (Burnham), along with Xianling Zhao, Ph.D., and colleagues, have clarified the role that retinoic acid plays in limb development. The study showed 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. The study was published online in the journal Current Biology.

In studies of mice and zebrafish, the team 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.

This video is not supported by your browser at this time.
Gregg Duester, Ph.D., talks about new research clarifying the role of retinoic acid in limb development. His research provides new insights into congenital limb defects. Credit: Burnham Institute for Medical Research

"For decades, it was thought that retinoic acid controlled limb patterning, such as defining the thumb as being different from the little finger," said Dr. 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. Dr. 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 and heart defects.

Source: Burnham Institute (news : web)

Explore further: A new way to treat colon cancer?

Related Stories

A new way to treat colon cancer?

October 10, 2006

Researchers at University of Utah's Huntsman Cancer Institute have discovered a new target for possible future colon cancer treatments – a molecule that is implicated in 85 percent of colon cancer cases.

Study shows how embryos regulate vitamin A derivatives

November 20, 2007

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 ...

Recommended for you

Mapping the protein universe

October 9, 2015

To understand how life works, figure out the proteins first. DNA is the architect of life, but proteins are the workhorses. After proteins are built using DNA blueprints, they are constantly at work breaking down and building ...

ZomBee Watch helps scientists track honeybee killer

October 9, 2015

While scientists have documented cases of tiny flies infesting honeybees, causing the bees to lurch and stagger around like zombies before they die, researchers don't know the scope of the problem.

Gene editing: Research spurs debate over promise vs. ethics

October 9, 2015

The hottest tool in biology has scientists using words like revolutionary as they describe the long-term potential: wiping out certain mosquitoes that carry malaria, treating genetic diseases like sickle-cell, preventing ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.