The urodele limb regeneration blastema. Determination and organization of the morphogenetic field.

The idea that the undifferentiated limb regeneration blastema of urodele amphibians is an undetermined and pluripotent structure is examined. A detailed review of the literature shows that this notion has no basis in fact. The data show that the morphogenetic potency of the blastema is restricted to its prospective significance and that this potency can be fully expressed when the blastema is transplanted either to a neutral location or to a regenerating organ of another type. Within this morphogenetic constraint, however, blastema cells have a histogenetic potency that is, at least in some cases, greater than their limb cell phenotype of origin. The morphogenetic responses of the regeneration field to discontinuities suggest that its autonomous determining relationships are based on the inheritance, from parent limb cells, of a graded set of mesodermal positional values specifying the pattern of the amputation plane, and a single epidermal external boundary value. The dividing mesenchymal cells of the blastema change positional value to erase any discontinuity between themselves and the epidermis, and the epidermis acts as a stop signal to inform the mesenchyme when the regenerate boundary has been reached. In vitro experiments suggest that changes in mesenchymal positional value in response to discontinuity can be interpreted in terms of gradients of cell-cell adhesivity, and they focus attention on the importance of molecular studies of blastema cell surfaces for our future understanding of regeneration and morphogenesis in general.