Tail regeneration in Xenopus laevis as a model for understanding tissue repair

Abstract

Augmentation of regenerative ability is a powerful strategy being pursued for the biomedical management of traumatic injury, cancer, and degeneration. While considerable attention has been focused on embryonic stem cells, it is clear that much remains to be learned about how somatic cells may be controlled in the adult organism. The tadpole of the frog Xenopus laevis is a powerful model system within which fundamental mechanisms of regeneration are being addressed. The tadpole tail contains spinal cord, muscle, vasculature, and other terminally differentiated cell types and can fully regenerate itself through tissue renewal--a process that is most relevant to mammalian healing. Recent insight into this process has uncovered fascinating molecular details of how a complex appendage senses injury and rapidly repairs the necessary morphology. Here, we review what is known about the chemical and bioelectric signals underlying this process and draw analogies to evolutionarily conserved pathways in other patterning systems. The understanding of this process is not only of fundamental interest for the evolutionary and cell biology of morphogenesis, but will also generate information that is crucial to the development of regenerative therapies for human tissues and organs.

Figure 1.

Example of Xenopus tail regeneration. (A) A schematic of the tail tip amputated in the tadpole. (B) A tadpole at 7 days of development. (C) A tadpole that has regenerated its tail (green arrow); several time-points during regeneration are shown in C′ (24 hpa), C″ (48 hpa), and C‴ (96 hpa). Blue stain in panel C″ indicates new tissue produced in the core of the tail regenerate. (D) A tadpole at 7 days that was treated with a V-ATPase inhibitor. The wound healed, but the tail did not regenerate (red arrowhead; purple line shows plane of amputation).

Figure 2.

A schematic of functional modules in tail regeneration. Injury triggers an immediate early response via still-unknown mechanisms. The early response includes the generation of a wound epithelium and rapid protein-level events. Next follows a set of physiological responses, including up-regulation of specific ion transporters (and the resulting bioelectric events) and programmed cell death of a specific cell group. Downstream lies a cascade of gene expression changes, resulting in the secretion of factors that modulate subsequent cell behaviors, such as mitotic rates and migration. The process completes when the system determines (via an unknown mechanism) that it has caught up to the correct tail size.