Morphogenesis of the vertebrate limb

Pattern formation in both the developing and the regenerating vertebrate limb can be understood in terms of the assignment of positional values to cells. The positional value may then control the selection of a course of cytodifferentiation as, say, muscle or cartilage. It is proposed that the proximodistal coordinate of positional value is extablished by a mechanism based on autonomous change with time in a 'progress zone' at the tip of the limb bud. The anteroposterior coordinate seems to be specified by a positional signal from an orgainzing region. Only cells in the progress zone respond to this signal. The change of character in the progress zone may be linked to cell division. It seems that each skeletal rudiment may initially be the same length, corresponding to the amount of tissue that leaves the progress zone during one cell cycle. The lengths on the skeletal elements are already specified shortly after exit from the progress zone, and are capable of very little regulation. The positional value may determine the pregramme of later growth. The relevance of the progress zone model to epimorphic regulation, and amphibian limb regeneration in particular, is discussed.