A bootstrap model for the proximodistal pattern formation in vertebrate limbs.

For the sequential determination of proximodistal structures during the outgrowth of vertebrate limbs, a 'bootstrap'-mechanism is proposed: by increasing feedback of more distally determined cells onto the production of a morphogen at the apical ectodermal ridge a successive increase of the morphogen concentration is achieved during outgrowth. The model accounts for the formation of a progress-zone at the limb tip, for the correct regeneration after truncation, for the presence and absence of proximodistal intercalation after certain graft experiments in amphibian limbs, for the tendency with which distal structures form in proximal position after certain experimental manipulations and for the intimate coupling of the anteroposterior and the proximodistal axes.