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Vitamin A's paradoxical role in influencing symmetry during embryonic development revealed

ervous system, the gastrointestinal tract, and other systems of the body.

Cells in the vicinity of the node are instructed to behave differently depending on whether they are on the left or right sides of the embryo. The action of retinoic acid makes sure that some of those cells ignore the left-right instructions and progress symmetrically.

Belmonte compares the node to a doorway. "Before embryonic stem cells enter the node, they don't have an orientation. Nor are they differentiated into specialized tissues -- such as heart or brain cells," he said. Once through the doorway, embryonic stem cells have their marching orders: they "know" where to locate themselves in the developing organism and what to differentiate into.

"Paradoxical," is the Salk scientists' description of retinoic acid signaling in the uniform ball of cells that is the early embryo, because its signaling influences both the asymmetric arrangement of organs and tissues in the interior of our bodies and the symmetrical pattern of the exterior of the trunk.

Belmonte and his Salk colleagues evaluated other signaling pathways that also influence pattern formation -- Wnt, fibroblast growth factor and Notch -- and found that none of them was responsible for coordinating the antero-posterior and left-right axes. However, blocking the retinoic acid pathway generated an uneven distribution of tissue on the right and left halves of the body. That is, somites (which give rise to the vertebrae and other body structures that are symmetrical) were unevenly distributed on the right and left axis. Normally, equal numbers of somites occur on each side.

In addition to improving scientific knowledge about early development, these research findings are relevant to the future development of treatments based on embryonic stem cells.

As explained by Salk senior research associate Angel Raya and co-first author of the Nature paper, the stem cells for such therapies wi
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Contact: Cathy Yarbrough
yarbrough@salk.edu
858-458-4100 x1290
Salk Institute
11-May-2005


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