Carbohydrate metabolism during vertebrate appendage regeneration: What is its role? How is it regulated?

Nick R Love,Enrique Amaya,Yaoyao Chen,Mathias Ziegler

doi:10.1002/bies.201300110

Abstract

We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon.

Highlights

Vertebrate appendage regeneration entails the reconstruction of outward growing tissue structures, including limbs, fins, digits, and tails
The regeneration process coordinates a variety of biological processes, all of which rely on molecules and energetic equivalents produced during cellular metabolism
We recently found that the expression of a substantial number of genes governing glucose metabolism was greatly altered during Xenopus tadpole tail regeneration [3]

Summary

Introduction

Vertebrate appendage regeneration entails the reconstruction of outward growing tissue structures, including limbs, fins, digits, and tails. Most biosynthetic pathways require carbon-containing precursor molecules generated directly or indirectly (though not exclusively) from carbohydrates such as glucose. For this reason, glucose utilization can be viewed as a convenient starting point to better understand. We recently found that the expression of a substantial number of genes governing glucose metabolism was greatly altered during Xenopus tadpole tail regeneration [3]. These data and others have led us to hypothesize that glucose metabolism and its regulation plays an essential role during vertebrate appendage regeneration. We take the opportunity to highlight the largely ignored role for carbohydrate metabolism during appendage regeneration and to encourage research aimed at better linking these two processes

The phases of Xenopus tail appendage regeneration

Cutting carbon emissions via glycolysis

Conclusions and prospects