Signal scaling during limb regeneration

Axolotls grow during their lives from 1 cm to 25 cm body length. Throughout this time, they can regenerate their limbs, and it is not yet known how the regeneration process is tuned so that the regenerated limb matches the size of the animal. This is an important question to study because it could give us insight into how to engineer adult size organs for humans. The regeneration process depends on cells from two opposite ends of the regenerating tissue to communicate with each other. It would be as if the regenerating tissue was a growing soccer field, where the goalies had to talk to each other. We want to know how the communication process is adapted to work over the smaller and the larger length scales. We do this by examining how travelling molecules change their diffusion properties, and how the sensitivity to these travelling communication molecules changes in depending on animal size.

The axolotl can regenerate its arm at any stage of its life. Regeneration occurs by a mass of stem cells forming at the amputation site. This stem cell zone is hundreds of times bigger than the stem cell zone that develops the limb in the embryo. Stem cells have to communicate with each other for the limb to develop and to regenerate. It was not known how cells can still communicate over a massively bigger distance during regeneration compared to development. We showed that the signalling from cells spread over a much bigger distance, according to the size of the axolotl. There is feedback regulation to make the signaling range appropriate for the size of the tissue. We are working on identifying the key factors that cause this signal spreading in regenerating tissue.