The human ARF tumor suppressor senses blastema activity and suppresses epimorphic tissue regeneration

摘要

Zebrafish are capable of remarkable feats of regeneration in which damaged or lost body parts can be replaced with exact replicas of the original. Humans cannot do this; so one major goal of regenerative medicine is to understand the basis of these differences. This could make it possible to regenerate damaged limbs, heart muscle and other tissues in people. A group of genes called tumor suppressor genes are critical for protecting us from cancer. However, they also limit the ability of cells to grow and divide, which are both important for regeneration processes. Differences in how organisms use tumor suppressor genes could possibly contribute to their differing abilities to regenerate body parts. A tumor suppressor gene called ARF plays an important role in protecting mammals from cancer, but it is not found in zebrafish and other animals that can regenerate body parts. Hesse et al. introduced the human ARF gene into zebrafish to investigate whether it has any effect on tissue regeneration. The experiments show that ARF is silent in growing and uninjured fish, but it is activated when it detects regeneration occurring after an injury. ARF drastically inhibits this process to the point that fish with the ARF gene cannot regenerate damaged tissue. The findings suggest that ARF mistakenly identifies regeneration as the formation of a tumor; therefore therapies that aim to induce regeneration in people may need to control the activity of this gene. Hesse et al.’s findings show that the specific tumor suppressor genes an organism has can affect its ability to regenerate. Future challenges will be to understand the situations in which ARF is able to interfere with tissue regeneration in mammals, and to learn how to manipulate this process.