Stem/progenitor cells in amphibian limb and spinal cord regeneration

Abstract

Amphibian regeneration may replace tissue via homotypic cells, dedifferentiation, transdifferentiation or stem cells. The mechanism may vary with life cycle stage. Expression of Notch signaling components suggests a role for stem cells. We examine the role of stem cells in regeneration-competent and incompetent stages of Xenopus laevis (clawed frog) tadpoles, juvenile and adult axolotls (the Mexican salamander Ambystoma mexicanum) and the regeneration-deficient axolotl mutant short-toes. Notch1 signaling is a key pathway in maintaining stem cell populations. The stem cell marker Musashi (Msi) is an RNA-binding protein inhibiting translation of Numb to maintain Notch1 signaling. Isoforms of Msi1 and Msi2 are expressed in temporal and spatial patterns that correlate with regeneration behavior. Msi-1 is expressed in specific tissue compartments in regeneration-competent Xenopus limb and spinal cord and decreases in incompetent tadpole and adult Xenopus tissues. Msi2 isoforms change between competent and incompetent Xenopus stages. Rapidly growing juvenile axolotls show high levels of Msi1 in both cord and limb, while intact adult axolotl tissues shows low levels of Msi1 that are upregulated following injury. Msi expression is also lost in limbs of the axolotl limb regeneration mutant short-toes, but maintained in the regeneration competent mutant spinal cord. Support: Indiana 21st Century Research and Technology Fund ; W.M. Keck Foundation.