How does regeneration work in planaria




















It would appear so. So where do the components needed to rebuild the cellular structures come from? In their search for the answer to this question, scientists have a population of small cells in their sights, namely the approximately five-micrometre-long neoblasts.

These cells are found almost everywhere in the planarian body and behave like stem cells: they divide, renew and can form the different cell types that have been lost as a result of amputation Fig. When the planarian loses a body part or discards its tail for reproduction, the neoblasts are reactivated and migrate to the wound. They divide there and their offspring form a blastema, in which — as a result of interplay between various extra- and intra-cellular factors — important differentiation and patterning processes take place.

Thanks to these processes, in turn, complex structures like the brain are formed. If the neoblasts are eliminated through radiation, for example, the planarian loses its ability to regenerate and dies within a few weeks. The fact that, following transplantation into an irradiated, neoblast-free worm, a single neoblast can produce all cell types and enable the host worm to regain its ability to regenerate shows that at least some neoblasts are pluripotent [2].

In healthy mammals, pluripotency, that is the ability of one cell to produce any given cell type found in an organism, e. Therefore, stable pluripotency in the adult organism is something special but not impossible as long as mechanisms exist for conserving this characteristic — as is clearly the case with the planarians. A Planarians are able to re-grow an entire head in a matter of a few days.

During regeneration, when a lot of new tissue has to be produced, they are able to generate a wide variety of cell types. The cell nuclei are marked in blue. Tissue-specific markers are marked in red, green and white. Figure 1A adapted from [1]. The preservation of pluripotency has been an important topic in stem cell research for years, and has mostly been examined up to now using isolated embryonic stem cells.

Important transcription factors that can induce and preserve pluripotency were discovered in the course of this research. So what can planarians contribute to the current research if their stem cells cannot be cultivated and reproduced outside of the body? This is precisely where the strength of the planarians as a model system in stem cell research lies: the combination they can offer of a natural extracellular environment and pluripotent stem cells.

Whereas cultivated stem cells are normally taken out of their natural environment and all important interactions with neighbouring cells and freely moving molecules are interrupted as a result, the stem cells in planarians can be observed and manipulated under normal conditions in vivo. Although planarians have been renowned as masters of regeneration and research objects for generations, they have undergone a genuine explosion in research interest in recent years.

In particular, the possibility of switching off specific genes through RNA interference RNAi and the availability of the genome sequence of Schmidtea mediterranea , a planarian species which is especially good at regenerating itself, have contributed to this surge in interest.

Hence, it is possible to examine which messenger RNAs mRNAs are produced that act as molecular templates for the production of proteins. However, the real work only starts here: the extent to which the presence of a particular mRNA also reflects the volume of protein that is active in the cell remains to be determined.

It is mainly the proteins in the form of enzymes, signalling molecules and structural elements, and not their mRNAs, that ultimately control the majority of cellular processes. In addition, their production using mRNA templates and their lifetime are precisely regulated processes and the frequency with which an mRNA arises cannot provide any information about these processes. The time has come, therefore, to develop experimental approaches for planarians that extend beyond gene expression analysis and lend greater significance to the subsequent regulatory processes.

Combined with the marking of proteins, quantitative mass spectrometry, which enables the identification of thousands of protein fragments based on their mass, provides a starting point here. The natural amino acid lysine, for example, contains six carbon atoms, each of which has six neutrons and six protons 12 C6 lysine.

However, a more detailed comparison of the targets of FoxA at different stages of planarian regeneration with the corresponding targets in other species could reveal the fundamental roles of this important transcription factor. This article is distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use and redistribution provided that the original author and source are credited. Article citation count generated by polling the highest count across the following sources: Crossref , PubMed Central , Scopus.

Planarian flatworms regenerate every organ after amputation. Adult pluripotent stem cells drive this ability, but how injury activates and directs stem cells into the appropriate lineages is unclear. Here we describe a single-organ regeneration assay in which ejection of the planarian pharynx is selectively induced by brief exposure of animals to sodium azide. To identify genes required for pharynx regeneration, we performed an RNAi screen of genes upregulated after amputation, using successful feeding as a proxy for regeneration.

We found that knockdown of 20 genes caused a wide range of regeneration phenotypes and that RNAi of the forkhead transcription factor FoxA , which is expressed in a subpopulation of stem cells, specifically inhibited regrowth of the pharynx. Selective amputation of the pharynx therefore permits the identification of genes required for organ-specific regeneration and suggests an ancient function for FoxA-dependent transcriptional programs in driving regeneration.

Learning more about the genes that allow flatworms to regenerate organs and tissue after amputation. Multiple mitogenic pathways capable of promoting mammalian cardiomyocyte CM proliferation have been identified as potential candidates for functional heart repair following myocardial infarction.

However, it is unclear whether the effects of these mitogens are species-specific and how they directly compare in the same cardiac setting. In 2D-cultured CMs from both species, and in highly mature 3D-engineered cardiac tissues generated from NRVMs, a constitutively active mutant form of the human gene Erbb2 cahErbb2 was the most potent tested mitogen.

Persistent expression of cahErbb2 induced CM proliferation, sarcomere loss, and remodeling of tissue structure and function, which were attenuated by small molecule inhibitors of Erk signaling. Cited 1 Views 15, Annotations Open annotations. The current annotation count on this page is being calculated.

Cite this article as: eLife ;3:e doi: Figure 1. Download asset Open asset. Image courtesy of Alex Lin and Bret Pearson. Asiatic Herpetol Res. The Schmidtea mediterranea genome database SmedGD. Dev Biol. Cold Spring Harb Perspect Biol. Morgan TH: Experimental studies of the regeneration of Planaria maculata. Arch Entw Mech Org. Article Google Scholar. Nat Rev Genet. Dev Cell. Cell Stem Cell. Syst Biol. Zhang P, Wake DB: Higher-level salamander relationships and divergence dates inferred from complete mitochondrial genomes.

Mol Phylogenet Evol. Download references. You can also search for this author in PubMed Google Scholar. Reprints and Permissions. BMC Biol 10, 88 Download citation. Received : 12 October Accepted : 02 November Published : 08 November Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. What is regeneration? Regenerative ability is broadly but unevenly distributed across species; why can't all animals replace tissues and organs after amputation?

Figure 1. Full size image. Why is the evolutionary origin of regeneration an important issue? Why are planarians a good model system to study regeneration?

Why study one particular species - Schmidtea mediterranea? Figure 2. Figure 3. What triggers regeneration? Which types of tissue can regenerate? What is the smallest fragment of tissue capable of regenerating a complete worm? Is some sort of specialized stem cell required for regeneration? What are neoblasts? Can a single neoblast generate a whole animal? Can neoblasts migrate?

Figure 4. Can the regenerative behavior of cells be traced to gene function in planarians? Figure 5. What lies ahead for planarians in particular and the field of regeneration in general? References 1. PubMed Article Google Scholar 5. Google Scholar 6. PubMed Article Google Scholar 8.

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