Basic Regeneration Research Using Model Organisms

We have a core interest in understanding the basis of the evolutionary divergence of regenerative capacity among species. Adult humans and other mammals do not have the ability to regenerate large portions of complex tissues after injury. In contrast, some lower vertebrates such as urodele amphibians (newts and salamanders) and zebrafish are endowed with extraordinary regenerative capacity. We are studying how evolutionary genetic changes account for these differences. We have approached this question by developing transgenic zebrafish models that are “humanized” with respect to their complement of tumor suppressor genes. We have found that the presence of the mammalian INK4a tumor suppressor locus which does not exist in fish, does not affect development but markedly compromises regenerative capacity, providing experimental evidence that the evolution of tumor suppression results in a trade-off at the expense of regenerative ability. We also have an ongoing interest in identification of novel evolutionary genetic differences and evaluation of their impact on regenerative capacity using cross-species genetic models.