The ZPA drew interest because it appeared, in some way, to control the formation of fingers and toes. But how? Some people believed that the cells in the ZPA made a molecule that then spread across the limb to instruct cells to make different fingers. The key proposal was that it was the concentration of this unnamed molecule that was the important factor. In areas close to the ZPA, where there is a high concentration of this molecule, cells would respond by making a pinky. In the opposite side of the developing hand, farther from the ZPA so that the molecule was more diffused, the cells would respond by making a thumb. Cells in the middle would each respond according to the concentration of this molecule to make the second, third, and fourth fingers.
This concentration-dependent idea could be tested. In 1979, Denis Summerbell placed an extremely small piece of foil between the ZPA patch and the rest of the limb. The idea was to use this barrier to prevent any kind of molecule from diffusing from the ZPA to the other side. Summerbell studied what happened to the cells on each side of the barrier. Cells on the ZPA side formed digits. Cells on the opposite side often did not form digits; if they did, the digits were badly malformed. The conclusion was obvious. Something was emanating from the ZPA that controlled how the digits formed and what they looked like. To identify that something, researchers needed to look at DNA.
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