First author

In the birth defect phocomelia, the long bones of the limbs are shorter than normal or, in the worst cases, do not develop at all, meaning that the hand or foot is attached directly to the shoulder or hip. Scientists studying the disorder — also seen in the 1950s and 1960s in the children of women who were prescribed the sedative thalidomide while pregnant — can mimic its characteristics by exposing the limb buds of developing chick embryos to irradiation.

Researchers had thought that the effects of both X-irradiation and thalidomide resulted in a defect in patterning — the correct laying-out of cells during development. In this model, a cell's identity is determined by the length of time it spends in a region near the tip of the developing limb bud. The thinking was that X-rays or thalidomide forced cells to stay too long in this region, called the progress zone, blocking their ability to form the bone cells of the limb regions closest to the shoulder and hip. But postdoc Jenna Galloway at Harvard Medical School in Boston, Massachusetts, and her colleagues have discovered that X-irradiation leads to problems with differentiation, the process by which progenitor cells assume specialized characteristics and functions (see page 400). She tells Nature more.

How does irradiation affect limb-bud cells?

During normal development the limb bud grows out and skeletal progenitor cells differentiate into bone cells. After we irradiated chick embryos, their limb buds lost some of the progenitor cells that become bone cells in the upper and middle parts of a limb, or proximal segments. These proximal segments still form, based on the presence of segment-specific, or patterning, markers. But when we looked for a differentiation marker for skeletal progenitors, we could not find it in the proximal segments. The marker was left only in the distal segments, the cells that would develop into hands or feet.

Were any results unexpected?

We were surprised that a major signal for limb growth and for telling cells to become distal cells was not disrupted by X-rays. This signal remained intact, which is why that part of the limb develops even after irradiation.

Did you encounter challenges?

When I started irradiating chick embryos, I put whole eggs into the X-ray machine. The embryos were fine, but did not get irradiated because of the shell. Then I tried cutting out a section of eggshell, leaving the embryo exposed, but it died. Finally, I cut a hole in the egg and placed shell pieces over part of the embryo to shield it, and that worked.