Wound epithelium function in axolotl limb regeneration.

Axolotls (Ambystoma mexicanum) have the ability to regenerate amputated limbs. The amputation surface is promptly covered by wound epithelium (WE), which is significant for the initiation of limb regeneration. In the present study, we investigated the formation of functional WE by analyzing the migration of WE after amputation. In the center of the amputation surface, epithelial cells migrated from surrounding epidermis to form WE. Therefore, WE around the center of the amputation surface was composed of the cells with dorsal, ventral, anterior and posterior identities, and we tentatively called this WE with radial positional identities, "central WE". When regeneration was complete, central WE became the epidermis around the bifurcation between the first and second digits. In addition, when the artificial rotation of epidermis was performed before amputation, all examined limbs regenerated normally, and central WE formed the epidermis at the bifurcation between first and second digits, similarly to that in normal regeneration. On the basis of our observations, the most important factor for the initiation of regeneration is considered to be the discontinuity of positional identity existing in WE. It is possible that the location of bifurcation between first and second digits is specified by the positional discontinuity in WE.