Attenuation of positional signalling in the chick limb by high doses of γ-radiation

Abstract

THE spatial pattern of cellular differentiation in the chick limb can be viewed in terms of positional information. For the antero–posterior axis of the wing, positional information seems to be specified by reference to a group of cells at the posterior margin of the limb bud—the zone of polarising activity (ZPA)^1–3. By grafting an additional ZPA to different positions along the antero–posterior axis, we found that structures form according to their distance from the nearest ZPA. For instance, digit 4 forms nearest to the ZPA, then digit 3, then digit 2. We suggested that cells might measure distance by means of a diffusible morphogen produced by the ZPA, the concentration of which falls as distance from the ZPA increases. The responding cells are able to interpret the concentration of the morphogen, and so behave according to their position. If it is the concentration of morphogen that specifies which digit shall form, then lowering the concentration of morphogen adjacent to the ZPA should result in digit 3 being formed next to the ZPA instead of digit 4. If the concentration is lowered still further, digit 2, and finally no additional digit should form next to the ZPA. We have obtained such an attenuation of positional signalling by treating the ZPA with increasing doses of γ radiation.