Abstract

BackgroundThe molecular mechanisms governing vertebrate appendage regeneration remain poorly understood. Uncovering these mechanisms may lead to novel therapies aimed at alleviating human disfigurement and visible loss of function following injury. Here, we explore tadpole tail regeneration in Xenopus tropicalis, a diploid frog with a sequenced genome.ResultsWe found that, like the traditionally used Xenopus laevis, the Xenopus tropicalis tadpole has the capacity to regenerate its tail following amputation, including its spinal cord, muscle, and major blood vessels. We examined gene expression using the Xenopus tropicalis Affymetrix genome array during three phases of regeneration, uncovering more than 1,000 genes that are significantly modulated during tail regeneration. Target validation, using RT-qPCR followed by gene ontology (GO) analysis, revealed a dynamic regulation of genes involved in the inflammatory response, intracellular metabolism, and energy regulation. Meta-analyses of the array data and validation by RT-qPCR and in situ hybridization uncovered a subset of genes upregulated during the early and intermediate phases of regeneration that are involved in the generation of NADP/H, suggesting that these pathways may be important for proper tail regeneration.ConclusionsThe Xenopus tropicalis tadpole is a powerful model to elucidate the genetic mechanisms of vertebrate appendage regeneration. We have produced a novel and substantial microarray data set examining gene expression during vertebrate appendage regeneration.

Highlights

  • The molecular mechanisms governing vertebrate appendage regeneration remain poorly understood

  • The Xenopus tadpole tail regeneration model has emerged as a powerful system for the study of vertebrate appendage regeneration

  • We created a transgenic Xenopus tropicalis line that transcribes eGFP under the control of the murine Tie-2 promoter

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Summary

Introduction

The molecular mechanisms governing vertebrate appendage regeneration remain poorly understood. Certain newts and salamanders completely regenerate limbs, tails, jaw, and eye lens following removal (reviewed in [4]) Frogs, during their larval tadpoles stages, have remarkable capacities to regenerate tissues following traumatic injury (reviewed in [5,6]). The Xenopus tadpole tail represents a interesting regenerating appendage, as it contains many axial and paraxial tissues, including the spinal cord, notochord, dorsal aorta, and skeletal muscle, of which all regenerate following amputation. Elegant studies using this model have uncovered important roles for FGF, Wnt, BMP and TGFb signaling during tail regeneration [9,10,11,12]. Given the complexity of regeneration, it is likely that many important genes and cellular processes during Xenopus tail regeneration remain unknown

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