Planaria regeneration

The evaluation of the ecotoxicological effects of the effluent after treatment with peracetic acid is relevant to help establish reference concentrations for the disinfection process and waste recovery. Therefore, the objective of this work was to evaluate the ecotoxicity of effluent from a bovine slaughterhouse treated with peracetic acid on Girardia tigrina. The toxicity bioassays for planaria were the acute test (LC50 ) and chronic assays: locomotion, regeneration, reproduction and fertility. The results showed that the effluent treated with peracetic acid showed less toxicity than the effluent without application of peracetic acid...

Adult planarians can regenerate the gut, eyes and even a functional brain. Proper identity and patterning of the newly formed structures require signals that guide and commit their adult stem cells. During embryogenesis, LIM-homeodomain (LIM-HD) transcription factors act in a combinatorial 'LIM code' to control cell fate determination and differentiation. However, our understanding about the role these genes play during regeneration and homeostasis is limited. Here, we report the full repertoire of LIM-HD genes in Schmidtea mediterranea ...

Germ cells (reproductive cells and their progenitors) give rise to the next generation in sexually reproducing organisms. The loss or removal of germ cells often leads to sterility in established research organisms such as the fruit fly, nematodes, frog, and mouse. The failure to regenerate germ cells in these organisms reinforced the dogma of germline-soma barrier in which germ cells are set-aside during embryogenesis and cannot be replaced by somatic cells. However, in stark contrast, many animals including segmented worms (annelids), hydrozoans, planaria, sea stars, sea urchins, and tunicates can regenerate germ cells...

Introduction: The MRL mouse strain is one of the few examples of a mammal capable of healing appendage wounds by regeneration, a process that begins with the formation of a blastema, a structure containing de-differentiating mesenchymal cells. HIF-1α expression in the nascent MRL wound site blastema is one of the earliest identified events and is sufficient to initiate the complete regenerative program. However, HIF-1α regulates many cellular processes modulating the expression of hundreds of genes...

Djeya1 (RKLAFRYRRIKELYNSYR) is a very effective cell penetrating peptide (CPP) that mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea . As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species-variable sites: 10, 13, and 16...

Planarians have become a powerful model system for stem cell research and regeneration. While the tool kit for mechanistic investigations has been steadily expanding over the last decade, robust genetic tools for transgene expression are still lacking. We describe here methods for in vivo and in vitro mRNA transfection of the planarian species Schmidtea mediterranea. These methods utilize the commercially available TransIT-mRNA transfection reagent to efficiently deliver mRNA encoding a synthetic nanoluciferase reporter...

The concentration of nanoplastics (NPs) is expected to increase in aquatic environments thus potentially threatening freshwater organisms through interactions with plastic particles that variously float, circulate in the water column or sink into the benthos. Studies into the mechanisms of any NP effects are still scarce, particularly with respect to the regenerative ability of biota for which there is no recognised model organism. The present study therefore aimed to investigate behavioural and regeneration responses of the freshwater planarian Girardia tigrina after 10 days exposed to along a gradient 0...

The regeneration capacity after an injury is critical to the survival of living organisms. In animals, regeneration ability can be classified into five primary types: cellular, tissue, organ, structure, and whole-body regeneration. Multiple organelles and signaling pathways are involved in the processes of initiation, progression, and completion of regeneration. Mitochondria, as intracellular signaling platforms of pleiotropic functions in animals, have recently gained attention in animal regeneration. However, most studies to date have focused on cellular and tissue regeneration...

Complex living agents consist of cells, which are themselves competent sub-agents navigating physiological and metabolic spaces. Behaviour science, evolutionary developmental biology and the field of machine intelligence all seek to understand the scaling of biological cognition: what enables individual cells to integrate their activities to result in the emergence of a novel, higher-level intelligence with large-scale goals and competencies that belong to it and not to its parts? Here, we report the results of simulations based on the TAME framework, which proposes that evolution pivoted the collective intelligence of cells during morphogenesis of the body into traditional behavioural intelligence by scaling up homeostatic competencies of cells in metabolic space...

Matrix metalloproteinases (MMPs) are members of a family of zinc-dependent metallopeptidase proteins that are widely found in plants, animals, and microorganisms. As the regulators of the extracellular matrix and basement membrane, MMPs play an important role in embryogenesis, development, innate immunity, and regeneration. However, the function of MMP family in planarian, a model for regeneration research, is still ambiguous. Here, we cloned 5 MMPs genes from Dugesia japonica and found that DjMMPA was associated with the process of regeneration, neoblasts cell maintenance confusion and destruction...

Regeneration abilities are widespread among animals and select species can restore any body parts removed by wounds that sever the major body axes. This capability of whole-body regeneration as exemplified in flatworm planarians, Acoels, and Cnidarians involves initial responses to injury, the assessment of wound site polarization, determination of missing tissue and programming of blastema fate, and patterned outgrowth to restore axis content and proportionality. Wnt signaling drives many shared and conserved aspects of the biology of whole-body regeneration in the planarian species Schmidtea mediterranea and Dugesia japonica, in the Acoel Hofstenia miamia, and in Cnidarians Hydra and Nematostella...

This review is a synopsis of the main points from the opening presentation by the authors in the Resolution of Inflammation session at the 8th European Workshop on Lipid Mediators held at the Karolinska Institute, Stockholm, Sweden, June 29th , 2022. Specialized pro-resolving mediators (SPM) promote tissue regeneration, control infections and resolution of inflammation. These include resolvins, protectins, maresins and the newly identified conjugates in tissue regeneration (CTRs). We reported mechanisms of CTRs in activating primordial regeneration pathways in planaria using RNA-sequencing...

Regeneration is initiated by wounding, but it is unclear how injury-induced signals precisely convey the identity of the tissues requiring replacement. In the planarian Schmidtea mediterranea, the first event in head regeneration is the asymmetric activation of the Wnt inhibitor notum in longitudinal body-wall muscle cells, preferentially at anterior-facing versus posterior-facing wound sites. However, the mechanism driving this early symmetry-breaking event is unknown. We identify a noncanonical Wnt11 and Dishevelled pathway regulating notum polarization, which opposes injury-induced notum-activating Wnt/β-catenin signals and regulates muscle orientation...

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Head-tail planaria morphologies are influenced by the electric potential differences across the animal's primary axis, as evidenced e.g. by voltage-sensitive dyes and functional experiments that create permanent lines of 2-headed but genetically wild-type animals. However, bioelectrical and biochemical models that make predictions on what would happen in the case of spatial chimeras made by tissue transplantation from different planaria (different species and head shapes) are lacking. Here, we use a bioelectrical model to qualitatively describe the effects of tissue transplantation on the shape of the r egenerated head...

Single-cell transcriptomics has revolutionised biology allowing the quantification of gene expression in individual cells. Since each single cell contains cell type specific mRNAs, these techniques enable the classification of cell identities. Therefore, single cell methods have been used to explore the repertoire of cell types (the single cell atlas) of different organisms, including freshwater planarians. Nowadays, planarians are one of the most prominent animal models in single cell biology. They have been studied at the single cell level for over a decade using most of the available single cell methodological approaches...

Extracellular matrix (ECM) is an important component of stem cell niche. Remodelling of ECM mediated by ECM regulators such as MMPs plays a vital role in stem cell function. However, the mechanisms that modulate the function of ECM regulators in the stem cell niche are understudied. Here, we explored the role of the transcription factor (TF), ETS-1 expressed in the cathepsin+ cell population in regulating the expression of the ECM regulator, mt-mmpA, thereby modulating basement membrane thickness. In planarians, the basement membrane around the gut/inner parenchyma is thought to act as a niche for pluripotent stem cells...

Regeneration experiments can produce complex phenotypes including morphological outcomes and gene expression patterns that are crucial for the understanding of the mechanisms of regeneration. However, due to their inherent complexity, variability between individuals, and heterogeneous data spreading across the literature, extracting mechanistic knowledge from them is a current challenge. Toward this goal, here we present protocols to unambiguously formalize the phenotypes of regeneration and their experimental procedures using precise mathematical morphological descriptions and standardized gene expression patterns...

Exposure to high levels of ionizing γ radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity and the re-establishment of stem cell activity in tissues damaged by ionizing radiation. We show that subthreshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally γ-irradiated tissues of the planarian flatworm Schmidtea mediterranea. Our findings reveal that DCS enhances DNA repair, transcriptional activity, and cell cycle entry in post-mitotic cells...

Planarians are free-living flatworms that emerged as a crucial model system to understand regeneration and stem cell biology. The ability to purify neoblasts, the adult stem cell population of planaria, through fluorescence-activated cell sorting (FACS) has tremendously increased our understanding of pluripotency, specialization, and heterogeneity. To date, the FACS-based purification methods for neoblasts relied on nuclear dyes that discriminate proliferating cells (>2N), as neoblasts are the only dividing somatic cells...