Organization of the morphogenetic field in regenerating amphibian limbs

Abstract

The amphibian limb is an example of a secondary embryonic field that can be reactivated during larval or adult life so that amputated parts are regenerated. Two major questions are: (1) what is the origin of the morphogenetic field of the regeneration blastema, and (2) what is the nature of this field and how does it specify the spatial pattern of blastemal redifferentiation? Evidence is analyzed here which leads to the following propositions: (1) the field is represented in latent form by properties of the mature limb cells, and these properties are activated and inherited by the blastemal cells after amputation and dedifferentiation. At the same time, the inherited field is sensitive to the mature stump tissues and its spatial organization can be altered by a stump pattern alien to the one from which it was derived. (2) The properties of the mesodermal limb tissues represent positional values that are arranged in gradients along the proximal-distal, anterior-posterior and dorsal-ventral axes. These properties allow dedifferentiated mesodermal cells to change their positional value to any value between their original one in the limb and the value of any neighboring cell after creation of a discontinuity. The direction of change is always from proximal to distal in the PD axis; it is uncertain as to whether change can take place only centripetally or both centripetally and centrifugally along the AP and DV axes. (3) Epidermal cells have the same positional value everywhere in the limb and act as the distal and circumferential boundaries up to which the mesodermal cells may change their positional values. The proximal boundary is represented by the level-specific properties of the mesodermal cells at the maximum extent of distal to proximal dedifferentiation. Normal regeneration can then be visualized as occurring in the following way. When deletions are made in the limb pattern, cells with widely different positional values are confronted. During regeneration, blastema cells increase in number and continually interact with their neighbors to adjust their positional values within the boundaries until discontinuities are eliminated. The multiple limbs resulting from rearrangement of stump tissue patterns can also be accounted for by using these propositions. It is suggested that positional information is encoded on the cell surface and/or in the extracellular matrix. © 1978 American Society of Zoologists.