Reviewing the Effects of Skin Manipulations on Adult Newt Limb Regeneration: Implications for the Subcutaneous Origin of Axial Pattern Formation

Newts are unique salamanders that can regenerate their limbs as postmetamorphic adults. In order to regenerate human limbs as newts do, it is necessary to determine whether the cells homologous to those contributing to the limb regeneration of adult newts also exist in humans. Previous skin manipulation studies in larval amphibians have suggested that stump skin plays a pivotal role in the axial patterning of regenerating limbs. However, in adult newts such studies are limited, though they are informative. Therefore, in this article we have conducted skin manipulation experiments such as rotating the skin 180° around the proximodistal axis of the limb and replacing half of the skin with that of another location on the limb or body. We found that, contrary to our expectations, adult newts robustly regenerated limbs with a normal axial pattern regardless of skin manipulation, and that the appearance of abnormalities was stochastic. Our results suggest that the tissue under the skin, rather than the skin itself, in the intact limb is of primary importance in ensuring the normal axial pattern formation in adult newt limb regeneration. We propose that the important tissues are located in small areas underlying the ventral anterior and ventral posterior skin