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Cell-death alternative model organisms: why and which?

Key Points

  • Cell death is one of the fundamental aspects of cell life. It is both multi-faceted, as there are several types of cell death, and complex, involving many molecules and several pathways.

  • Our representation of cell death is defined by the few model organisms studied so far. This representation includes caspase-dependent apoptosis and a variety of various, less well defined caspase-independent, non-apoptotic types of cell death.

  • The use of alternative model organisms could modify this representation. In particular, it might help to reveal conserved molecules and phenomena that are less prominent in the classical model organisms.

  • Alternative model organisms can be chosen as a function of their ability to answer some of the remaining questions in the cell-death field. The criteria for choice include, for example, their phylogenetic position, as well as some biological properties and their genetic tractability.

  • Examples of possible alternative model organisms to study cell death include zebrafish, Hydra, Podospora, Dictyostelium and Volvox, but investigating cell death in any new model organism is likely to provide new insights.

Abstract

Classical model organisms have helped greatly in our understanding of cell death but, at the same time, might have constrained it. The use of other, non-classical model organisms from all biological kingdoms could reveal undetected molecular pathways and better-defined morphological types of cell death. Here we discuss what is known and what might be learned from these alternative model systems.

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Figure 1: A simplified view of the main pathways of caspase-dependent cell death.
Figure 2: Phylogenetic tree of model organisms used to study cell death.
Figure 3: Zebrafish.
Figure 4: Hydra.
Figure 5: Podospora anserina.
Figure 6: Dictyostelium discoideum.
Figure 7: Volvox.

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Acknowledgements

Many thanks to M. Bof, A. Böttger, C. Clavé, P. Herbomel, D. Kirk, G. Klein, L. Leserman, M.-F. Luciani, C. Roisin and M. Satre for some of the illustrations, helpful suggestions and unpublished data. We acknowledge the Institute National de la Santé et de la Recherche Medicale, the Centre National de la Recherche Scientifique, the Commissariat à l'Energie Atomique, the Association pour la Recherche contre le Cancer, the Ministère de la Recherche et de la Technologie and the European Community for additional support. Also, we wish to apologize to the many that should have been cited here if space had allowed.

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Correspondence to Pierre Golstein.

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DATABASES

LocusLink

Apaf1

BCL2

ced-3

ced-4

DAXX

Reaper

FURTHER INFORMATION

Zebrafish Information Network

Zebrafish Information Server

Cnidaria Home Page

Podospora anserina web page

dictyBase

BioImages: The Virtual Field Guide, Volvox

Protist Information server, Volvox

Glossary

CASPASE

A subfamily of cysteine proteases. Caspases have a catalytic cysteine residue and recognize a tetrapeptide on their substrate that always includes aspartic acid at position 1.

TUNEL

A technique that enables the detection of DNA fragmentation at the cellular level. Fragmented DNA generates many free DNA ends and, using terminal transferase, these can be labelled with tagged nucleotides, which can be secondarily detected using appropriate reagents.

SPHINGOLIPID

A derivative of the long-chain amino diol sphingosine. Its structure is similar to a glycerol-based phospholipid, with a polar head group as well as two hydrophobic hydrocarbon chains (one is the sphingosine and the other is a fatty acid chain).

PARA-CASPASE

Protein that shows only weak homology to caspases, and is found in metazoans and Dictyostelium.

META-CASPASE

Protein that shows only weak homology to caspases, and is found in plants, fungi and protozoa.

MORPHOLINO

A chemically modified oligonucleotide that behaves as an antisense RNA analogue and which is used to interfere with gene function.

NEMATOCYTE

Stinging cell found in Hydra that is used for capturing prey and for defence. Nematocytes differentiate from interstitial cells and are mainly found in the tentacles.

ARTICLE

A multinucleated segment of a filament limited by septa in filamentous fungi.

PROTOPLAST

For a cell with an external cell wall, the protoplast is what is left (protoplasm and plasma membrane) after the cell wall has been removed.

HETEROKARYON

A cell with two or more genetically different nuclei, produced by the fusion of genetically different cells.

AXENIC

The ability to grow on an artificial medium under laboratory conditions that eliminate all other living organisms from the medium.

SPHEROID

A ball-like coherent unit that constitutes the adult form of Volvox. This spheroid is composed of two cell types: small biflagellated somatic cells at the periphery, and large internal gonidia that are devoted to reproduction.

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Golstein, P., Aubry, L. & Levraud, JP. Cell-death alternative model organisms: why and which?. Nat Rev Mol Cell Biol 4, 798–807 (2003). https://doi.org/10.1038/nrm1224

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