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First published online August 7, 2009
doi: 10.1242/10.1242/dev.035501

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Early requirement of Hyaluronan for tail regeneration in Xenopus tadpoles

Center for Aging and Regeneration, Center for Cell Regulation and Pathology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.

^* Author for correspondence (jlarrain{at}bio.puc.cl)

Accepted 22 June 2009

Tail regeneration in Xenopus tadpoles is a favorable model system to understand the molecular and cellular basis of tissue regeneration. Although turnover of the extracellular matrix (ECM) is a key event during tissue injury and repair, no functional studies to evaluate its role in appendage regeneration have been performed. Studying the role of Hyaluronan (HA), an ECM component, is particularly attractive because it can activate intracellular signaling cascades after tissue injury. Here we studied the function of HA and components of the HA pathway in Xenopus tadpole tail regeneration. We found that transcripts for components of this pathway, including Hyaluronan synthase2 (HAS2), Hyaluronidase2 and its receptors CD44 and RHAMM, were transiently upregulated in the regenerative bud after tail amputation. Concomitantly, an increase in HA levels was observed. Functional experiments using 4-methylumbelliferone, a specific HAS inhibitor that blocked the increase in HA levels after tail amputation, and transgenesis demonstrated that the HA pathway is required during the early phases of tail regeneration. Proper levels of HA are required to sustain proliferation of mesenchymal cells in the regenerative bud. Pharmacological and genetic inhibition of GSK3β was sufficient to rescue proliferation and tail regeneration when HA synthesis was blocked, suggesting that GSK3β is downstream of the HA pathway. We have demonstrated that HA is an early component of the regenerative pathway and is required for cell proliferation during the early phases of Xenopus tail regeneration. In addition, a crosstalk between HA and GSK3β signaling during tail regeneration was demonstrated.

Key words: Xenopus, Appendage regeneration, Hyaluronan, GSK3β

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