Abstract

BackgroundThe proper balance of cell division and cell death is of crucial importance for all kinds of developmental processes and for maintaining tissue homeostasis in mature tissues. Dysregulation of this balance often results in severe pathologies, such as cancer. There is a growing interest in understanding the factors that govern the interplay between cell death and proliferation under various conditions. Survivin and mortalin are genes that are known to be implicated in both mitosis and apoptosis and are often expressed in tumors.ResultsThe present study takes advantage of the ability of the sea cucumber Holothuria glaberrima Selenka, 1867 (Holothuroidea, Aspidochirota) to discard its viscera and completely regrow them. This visceral regeneration involves an extensive expression of survivin and mortalin transcripts in the gut mesothelium (the outer tissue layer of the digestive tube), which coincides in time with drastic de-differentiation and a burst in cell division and apoptosis. Double labeling experiments (in situ hybridization combined with TUNEL assay or with BrdU immunohistochemistry) suggest that both genes support cell proliferation, while survivin might also be involved in suppression of the programmed cell death.ConclusionsVisceral regeneration in the sea cucumber H. glaberrima is accompanied by elevated levels of cell division and cell death, and, moreover, involves expression of pro-cancer genes, such as survivin and mortalin, which are known to support proliferation and inhibit apoptosis. Nevertheless, once regeneration is completed and the expression pattern of both genes returns to normal, the regrown digestive tube shows no anomalies. This strongly suggests that sea cucumbers must possess some robust cancer-suppression mechanisms that allow rapid re-growth of the adult tissues without leading to runaway tumor development.

Highlights

  • The proper balance of cell division and cell death is of crucial importance for all kinds of developmental processes and for maintaining tissue homeostasis in mature tissues

  • The baculovirus IAP repeat (BIR) domain is known to be essential both for apoptosis inhibition and mitosis-related functions, while the coiled-coil motif is thought to allow survivin protein to interact with microtubules of the mitotic spindle [13,22]

  • All developmental events including embryogenesis, postnatal cell turnover, tumor formation, and regeneration rely on the balance between cell division and cell death

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Summary

Introduction

The proper balance of cell division and cell death is of crucial importance for all kinds of developmental processes and for maintaining tissue homeostasis in mature tissues Dysregulation of this balance often results in severe pathologies, such as cancer. The regenerating digestive tube of sea cucumbers provides a unique experimental model for studying processes of extensive cell activation and proliferation without uncontrolled tumor formation. Another experimental advantage of this system is that the injury occurs by autotomy in pre-determined regions [3,4], i.e., in a very consistent and repeatable manner, which excludes variation between animals in the extent and severity of the trauma. The molecular machinery underlying such an extraordinary plasticity in postembryonic tissues remains largely unknown

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