Homeobox-Containing Genes in Limb Regeneration

Abstract

Early investigations established an important role for homeobox-containing genes in the initiation of regeneration, as well as in the later pattern formation events leading to a new limb. The recent increased research on the mechanisms of regeneration, along with the fact that urodele amphibians provide the only opportunity to understand how vertebrates can regenerate their limbs, has led to a renewed interest in the functioning of this important group of genes during salamander limb regeneration. It appears that all vertebrates, including humans, have impressive regenerative abilities as embryos; however, all but urodeles lose much of these abilities as development proceeds. In contrast, cells in adult urodeles are unique in their ability to revert to an embryonic state (dedifferentiate) in order to recapitulate embryo-genesis, Consequently, urodeles are the only adult vertebrates that can completely and perfecdy regenerate entire limbs, and thus they offer a unique opportunity to gain critical insights for future advances in regenerative medicine. Much data indicate that a large number of homeobox genes play important roles in the initiation and regulation of limb regeneration. In some instances, the regulatory mechanisms controlling homeobox gene expression appear comparable to what is observed in developing limbs; whereas, in others they different dramatically. In spite of differences in spatial and temporal expression patterns, homeobox gene function is conserved in both regeneration and development. Research on the role of homeobox genes is poised to move forward, particularly in the context of the early stages that are unique to regeneration, and thus are critical in achieving the goal of inducing human regeneration. These efforts will be possible because of the new genetic resources for research utilizing the axolod as a model system.