Initiating a regenerative response; cellular and molecular features of wound healing in the cnidarian Nematostella vectensis

Timothy Q Dubuc,Mark Q Martindale,Nikki Traylor-Knowles

doi:10.1186/1741-7007-12-24

Abstract

BackgroundWound healing is the first stage of a series of cellular events that are necessary to initiate a regenerative response. Defective wound healing can block regeneration even in animals with a high regenerative capacity. Understanding how signals generated during wound healing promote regeneration of lost structures is highly important, considering that virtually all animals have the ability to heal but many lack the ability to regenerate missing structures. Cnidarians are the phylogenetic sister taxa to bilaterians and are highly regenerative animals. To gain a greater understanding of how early animals generate a regenerative response, we examined the cellular and molecular components involved during wound healing in the anthozoan cnidarian Nematostella vectensis.ResultsPharmacological inhibition of extracellular signal-regulated kinases (ERK) signaling blocks regeneration and wound healing in Nematostella. We characterized early and late wound healing events through genome-wide microarray analysis, quantitative PCR, and in situ hybridization to identify potential wound healing targets. We identified a number of genes directly related to the wound healing response in other animals (metalloproteinases, growth factors, transcription factors) and suggest that glycoproteins (mucins and uromodulin) play a key role in early wound healing events. This study also identified a novel cnidarian-specific gene, for a thiamine biosynthesis enzyme (vitamin B synthesis), that may have been incorporated into the genome by lateral gene transfer from bacteria and now functions during wound healing. Lastly, we suggest that ERK signaling is a shared element of the early wound response for animals with a high regenerative capacity.ConclusionsThis research describes the temporal events involved during Nematostella wound healing, and provides a foundation for comparative analysis with other regenerative and non-regenerative species. We have shown that the same genes that heal puncture wounds are also activated after oral-aboral bisection, indicating a clear link with the initiation of regenerative healing. This study demonstrates the strength of using a forward approach (microarray) to characterize a developmental phenomenon (wound healing) at a phylogenetically important crossroad of animal evolution (cnidarian-bilaterian ancestor). Accumulation of data on the early wound healing events across numerous systems may provide clues as to why some animals have limited regenerative abilities.

Highlights

Wound healing is the first stage of a series of cellular events that are necessary to initiate a regenerative response
Among the results reported here, we found that the inhibition of extracellular signal-regulated kinases (ERK) signaling blocked both wound healing and regeneration in Nematostella
Cellular events orchestrated during wound healing of Nematostella vectensis Punctures were formed by passing a glass needle through ectodermal and endodermal layers of the aboral portion of animals (Figure 1C) and took approximately six hours to heal (Figure 2A)

Summary

Introduction

Wound healing is the first stage of a series of cellular events that are necessary to initiate a regenerative response. Regeneration experiments where wound healing was allowed to proceed but cellular proliferation was chemically blocked can be rescued by re-injuring the same untreated tissue, triggering mitosis and regeneration [16] This suggests that wound healing acts as an initiator of regeneration in Nematostella, where the onset of proliferation may serve as an important transition between wound healing and a regenerative response (Figure 1A). The high regenerative capacity and key phylogenetic position of cnidarians provide a unique opportunity to study the basic mechanism underlying animal wound repair. This type of study is of great interest in comparison to other highly regenerative animals (to see similarities) and in comparison to animals that lack the capacity to regenerate (to see differences). Studying new systems with forward approaches provides unique opportunities for gene discovery

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Discussion

Conclusion