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  • Review Article
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Bridging the regeneration gap: genetic insights from diverse animal models

Nature Reviews Genetics volume 7, pages 873–884 (2006)Cite this article

Key Points

  • Regeneration is widely distributed among the various phyla that compose the animal kingdom, including vertebrates.

  • Limitations in the ability to interrogate this attribute at the molecular level have hampered efforts to delineate the mechanistic underpinnings of regeneration.

  • Loss-of-function screens (using RNAi) and gain-of-function assays (transgenesis) have recently been introduced to study molecular pathways in traditional model systems of regeneration, overcoming past limitations to probe their biology at the molecular level.

  • Studies in simple animals such as hydra and planarians are beginning to contribute to our understanding of tissue remodelling and adult somatic stem-cell regulation in animals.

  • Studies in mammals and other vertebrates have highlighted central roles for the activation of specific signalling pathways in the processes of organ and limb regeneration.

  • Comparative studies of regenerative processes among the various animals that are currently under investigation could provide important insights into the permissive and non-permissive mechanisms that underlie regenerative competence.

  • Such information is likely to yield fundamental insights for our understanding of metazoan biology, and to expand the repertoire of therapeutic possibilities in the fields of regenerative medicine.

Abstract

Significant progress has recently been made in our understanding of animal regenerative biology, spurred on by the use of a wider range of model organisms and an increasing ability to use genetic tools in traditional models of regeneration. This progress has begun to delineate differences and similarities in the regenerative capabilities and mechanisms among diverse animal species, and to address some of the key questions about the molecular and cell biology of regeneration. Our expanding knowledge in these areas not only provides insights into animal biology in general, but also has important implications for regenerative medicine and stem-cell biology.

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Figure 1: Regeneration in multicellular organisms — phylogenetic distribution and model species.
Figure 2: Basic mechanisms of regeneration.
Figure 3: Basic steps in the formation of regeneration blastemas in vertebrates and invertebrates.
Figure 4: An RNAi screen for genes with functions in planarian regeneration.
Figure 5: Common signalling pathways in the induction of regeneration in diverse species.

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Acknowledgements

A.S.A. thanks the National Institutes of Health and the National Institute of General Medical Sciences for supporting work on planarian regeneration, and the National Human Genome Research Institute for supporting the sequencing of the S. mediterranea genome. P.A.T. would like to thank the National Institutes of Health and the National Eye Institute for supporting eye regeneration research.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, University of Utah School of Medicine, Deptartment of Neurobiology and Anatomy, Salt Lake City, 84132, Utah, USA

    Alejandro Sánchez Alvarado

  2. Department of Biology and Center for Tissue Regeneration and Engineering, University of Dayton, Dayton, 45469, Ohio, USA

    Panagiotis A. Tsonis

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  1. Alejandro Sánchez Alvarado
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Correspondence to Alejandro Sánchez Alvarado.

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Glossary

Dedifferentiation

The process by which a terminally differentiated cell loses its tissue-specific characteristics and becomes undifferentiated. Dedifferentiated cells can either re-differentiate into cells of their original type or to a cell of different lineage.

Transdifferentiation

The process by which a terminally differentiated cell dedifferentiates and then re-differentiates to a cell of a different lineage, for example, the transdifferentiation of iris pigment epithelial cells to lens during newt lens regeneration.

Diploblast

An organism that is derived from two primary germ layers: the ectoderm and the endoderm.

Triploblast

An organism that is derived from three primary germ layers: the ectoderm, the mesoderm and the endoderm.

Organizer

The regions within an embryo that control development and differentiation.

Autophagy

A nutritionally and developmentally regulated process that is involved in the intracellular destruction of endogenous proteins and the removal of damaged organelles.

Mixoploid

An organism that contains cells which are of different ploidy, for example, diploid and polyploid.

Argonaute/PIWI family

Members of this protein family contain PAZ and PIWI domains, which are involved, respectively, in binding small RNAs and mediating silencing, either by cleavage of mRNAs or through inhibition of translation.

Schwann cells

Non-neuronal cells that mainly provide myelin insulation to axons in the peripheral nervous system of jawed vertebrates.

Neotenous animals

Animals that, as adults, retain traits that are usually seen only in juveniles.

Morpholino

A chemically modified oligonucleotide that behaves as an antisense RNA analogue and can therefore be used to interfere with gene function.

Forebrain

The rostral-most portion of the brain.

Complement system

A biochemical cascade that is involved in innate immunity: the first line of defence that helps to clear pathogens from an organism.

Hippocampus

A part of the brain that is located inside the temporal lobe. It forms part of the limbic system and has a role in memory and spatial navigation.

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Alvarado, A., Tsonis, P. Bridging the regeneration gap: genetic insights from diverse animal models. Nat Rev Genet 7, 873–884 (2006). https://doi.org/10.1038/nrg1923

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