Salamander limbs regenerate by forming a blastema of mesenchyme-like cells derived by the dedifferentiation of the cell types at the amputation surface. A variety of grafting experiments have shown that the amphibian limb regeneration blastema is a self-organizing system; that is, it contains all the positional information required for pattern formation independent of adjacent differentiated tissues (D.L. Stocum and others). At the same time, the blastema cells are dependent on nerves, as well as the apical epidermal cap, for survival and proliferation factors. Other grafting experiments show that contiguous blastema cells can sense discontinuities in positional identity and reduce them by intercalary regeneration until a normal neighbor map of positional identities is re-established. This has led to the development of a model of regeneration in which missing positional identities are intercalated within circumferential, proximal and distal boundaries. Positional identity is associated with axial differentials in blastema cell adhesivity. Manipulation of positional identity by retinoic acid has to date revealed one cell surface molecule that appears to be involved in creating a differential gradient of positional adhesivity in the proximodistal axis. The circumferential and proximal boundary positional identities of blastema cells are inherited from parent limb cells as they dedifferentiate. However, it is not known how the distal boundary of the proximodistal axis is re-established. An idea of how this might take place will be presented. Lastly, a number of ideas for modeling aspects of limb regeneration will be presented. Supported by the Indiana 21st Century Research and Technology Fund.
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