Role of Wound Epidermis and Apical Epidermal Cap

Earlier described that amputation, the stump epidermal cells at the wound edge migrate over and quickly cover the wound to from a multilayered apical epidermal cap. The formation of this cap depends upon the early innervations of the wound epidermis through nerve fibers. The cap fails to make if the limb is denervated before or immediately after amputation. If this cap is removed regeneration fails to take place. If an additional cap is grafted on the emergent blastema it induces regeneration of supernumerary limb. Thus the apical epidermal cap formed via wound epidermis is necessary for permitting regeneration. Any other epidermis grafted on the wound surface does not make the apical cap and does not support regeneration. This shows that only the apical cap that developed from the wound epithelium could promote and maintain regeneration of the limb.

In the non-regenerating amputated limb-stumps of older tadpoles and adults of frogs, the characteristic apical epidermal cap does not develop and thus regeneration does not take place. Experimental results point out that wound epidermis stimulates dedifferentiation and mitosis in the underlying cells arising from stump tissue so inducing the formation and growth of the blastema and the consequent regeneration of the limb. The blastema cells in the zone instantaneously adjacent to the apical cap remain in an undifferentiated and proliferating state, while those proximal to this zone start to differentiate. In this way proximal distal pattern of re-differentiation of blastema cells is controlled through the epidermal cap. You may recall that the apical ectodermal ridge (AER) of the embryonic limb bud also plays a identical role in allowing distal outgrowth of the limb. Both the AER in, embryonic limb development and apical cap of the regenerating limb stimulate cellular proliferation in cells situated beneath them and keep them from differentiating that enables differentiation of limb tissues in a proximo-distal sequence.