Outline of our study
Urodele amphibians, such as newts and axolotls, can regenerate their missing body parts. In contrast, we cannot regenerate "body parts". Our ultimate goal is to understand the tricks of their higher regeneration ability and to apply their tricks onto higher vertebrates.
Limb regeneration study had been a major of developmental biology in past. However, the field was getting smaller and smaller because the field of limb regeneration failed to make a breakthrough for a long time. To break up that situation, we have developed a new experimental system called the accessory limb model (ALM) (Endo et al., 2004, Dev. Biol., our group 2007~2014, Dev. Biol.). ALM becomes a great power to force the stuck clock hands moving forward.
Limb regeneration is controlled by nerves in most parts. Especially, nerve is essential in the induction phase of limb regeneration. We discovered that nerves induce “a regeneration blastema” when it is present in wounded region. If nerves are absent in wounded region, even axolotl cannot regenerated. The denervated axolotl limb is just like a human limb. Nerves have been considered to secrete some trophic molecules to induce a blastema from an amputation plane. Therefore, if nerve factors are revealed, it will be possible to apply it in a human limb to investigate possibility of blastema induction by the determined nerve factors. And possibly, it can be called as a regenerative medicine in higher vertebrates.
To identify the nerve factors, we have developed a brand-new experimental model, the accessory limb mode (ALM). The ALM is a simple experimental system. First, a piece of skin is removed and then, nerves are taken to the wounded region. Such procedure is sufficient to induce a blastema in a limb. Nerves play a role in transforming skin wound healing to blastema formation. However, to obtain a patterned limb, an additional procedure is necessary. Skin grafting from a contralateral side of a limb to a nerve deviated wound gives a well pattern limb. The meaning of the skin graft is assumed to provide variety of positional values. Positional values are sort of "address" of cells. A blastema lacking in the positional values cannot draw a well coordinate map of a limb. This causes defectiveness in patterning. But this is still just a hypothesis. Positional values and meaning of a skin graft should be described in future. Nerves, skin grafting and skin wounding can result in induction of a limb in anywhere within a limb. This experimental system has contributed to understand the induction phase of a blastema in amphibians.
Our lab is aiming to understand the induction mechanisms of limb regeneration, including in determination of nerve factors. And we have tried to apply pur insights onto limbs in higher vertebrates. Currently, we started using frogs and chicks in our experiments.
Satoh Akira, Ph.D, Associate Prof.
address; 3-1-1, tsushimanaka, kitaku, okayama, 700-8530, Japan.