Implication of two different regeneration systems in limb regeneration

Limb regeneration is a representative phenomenon of organ regeneration in urodele amphibians, such as an axolotl. An amputated limb starts regenerating from a remaining stump (proximal) to lost finger tips (distal). In the present case, proximal−distal (PD) reorganization takes place in a regenerating tissue, called a blastema. It has been a mystery how an induced blastema recognizes its position and restores an exact replica of missing parts. Recently, a new experimental system called the accessory limb model (ALM) has been established. The gained ALM phenotypes are demanding to reconsider the reorganization PD positional values. Based on the ALM phenotype, it is reasonable to hypothesize that reorganization of positional values has a certain discontinuity and that two different regeneration systems cooperatively reorganize the PD axis to restore an original structure. In this review, PD axis reestablishments are focused on limb regeneration. Knowledge from ALM studies in axolotls and Xenopus is providing a novel concept of PD axis reorganization in limb regeneration.