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  • 1
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    Ectoderm to mesoderm lineage switching during axolotl tail regeneration (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-12-10
    Description: Foreign environments may induce adult stem cells to switch lineages and populate multiple tissue types, but whether this mechanism is used for tissue repair remains uncertain. Urodele amphibians can regenerate fully functional, multitissue structures including the limb and tail. To determine whether lineage switching is an integral feature of this regeneration, we followed individual spinal cord cells live during tail regeneration in the axolotl. Spinal cord cells frequently migrate into surrounding tissue to form regenerating muscle and cartilage. Thus, in axolotls, cells switch lineage during a real example of regeneration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Echeverri, Karen -- Tanaka, Elly M -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):1993-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471259" target="_blank"〉PubMed〈/a〉
    Keywords: Ambystoma/physiology ; Animals ; Cell Differentiation ; *Cell Lineage ; Cell Movement ; Chondrocytes/*cytology/physiology ; Ectoderm/cytology ; Glial Fibrillary Acidic Protein/genetics ; Green Fluorescent Proteins ; Luminescent Proteins/genetics ; Mesoderm/cytology ; Muscle Cells/*cytology/physiology ; Neuroglia/physiology ; Neurons/cytology/physiology ; *Regeneration ; Spinal Cord/*cytology/physiology ; Stem Cells/*physiology ; Tail/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Cells keep a memory of their tissue origin during axolotl limb regeneration (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-07-03
    Description: During limb regeneration adult tissue is converted into a zone of undifferentiated progenitors called the blastema that reforms the diverse tissues of the limb. Previous experiments have led to wide acceptance that limb tissues dedifferentiate to form pluripotent cells. Here we have reexamined this question using an integrated GFP transgene to track the major limb tissues during limb regeneration in the salamander Ambystoma mexicanum (the axolotl). Surprisingly, we find that each tissue produces progenitor cells with restricted potential. Therefore, the blastema is a heterogeneous collection of restricted progenitor cells. On the basis of these findings, we further demonstrate that positional identity is a cell-type-specific property of blastema cells, in which cartilage-derived blastema cells harbour positional identity but Schwann-derived cells do not. Our results show that the complex phenomenon of limb regeneration can be achieved without complete dedifferentiation to a pluripotent state, a conclusion with important implications for regenerative medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kragl, Martin -- Knapp, Dunja -- Nacu, Eugen -- Khattak, Shahryar -- Maden, Malcolm -- Epperlein, Hans Henning -- Tanaka, Elly M -- England -- Nature. 2009 Jul 2;460(7251):60-5. doi: 10.1038/nature08152.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571878" target="_blank"〉PubMed〈/a〉
    Keywords: Ambystoma/embryology/*physiology ; Animals ; Animals, Genetically Modified ; Cartilage/cytology ; Cell Differentiation/radiation effects ; Cell Lineage/*physiology/radiation effects ; Cell Movement ; Epidermis/cytology ; Extremities/*growth & development/innervation ; Muscles/cytology ; Organ Specificity ; Regeneration/*physiology ; Schwann Cells/cytology ; Tendons/cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Regenerative biology: Skin, heal thyself (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-09-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanaka, Elly M -- England -- Nature. 2012 Sep 27;489(7417):508-10. doi: 10.1038/489508a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23018959" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Male ; Murinae/*physiology ; Regeneration/*physiology ; Skin/*injuries ; *Skin Physiological Phenomena
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Progressive specification rather than intercalation of segments during limb regeneration (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-12-18
    Description: An amputated salamander limb regenerates the correct number of segments. Models explaining limb regeneration were largely distinct from those for limb development, despite the presence of common patterning molecules. Intercalation has been an important concept to explain salamander limb regeneration, but clear evidence supporting or refuting this model was lacking. In the intercalation model, the first blastema cells acquire fingertip identity, creating a gap in positional identity that triggers regeneration of the intervening region from the stump. We used HOXA protein analysis and transplantation assays to show that axolotl limb blastema cells acquire positional identity in a proximal-to-distal sequence. Therefore, intercalation is not the primary mechanism for segment formation during limb regeneration in this animal. Patterning in development and regeneration uses similar mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roensch, Kathleen -- Tazaki, Akira -- Chara, Osvaldo -- Tanaka, Elly M -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1375-9. doi: 10.1126/science.1241796.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Deutsche Forschungsgemeinschaft (DFG)-Center for Regenerative Therapies Dresden, Technische Universitat Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24337297" target="_blank"〉PubMed〈/a〉
    Keywords: Ambystoma mexicanum ; Animals ; Body Patterning ; Extremities/anatomy & histology/*physiology ; Homeodomain Proteins/*metabolism ; Molecular Sequence Data ; *Regeneration
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Artificial neural tubes [Developmental Biology] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-11-02
    Description: Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemical and biophysical extracellular matrix (ECM) factors in promoting multicellular growth and reorganization. Here,...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    FGF8 and SHH substitute for anterior-posterior tissue interactions to induce limb regeneration (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-04-28
    Description: In salamanders, grafting of a left limb blastema onto a right limb stump yields regeneration of three limbs, the normal limb and two 'supernumerary' limbs. This experiment and other research have shown that the juxtaposition of anterior and posterior limb tissue plus innervation are necessary and sufficient to induce complete limb regeneration in salamanders. However, the cellular and molecular basis of the requirement for anterior-posterior tissue interactions were unknown. Here we have clarified the molecular basis of the requirement for both anterior and posterior tissue during limb regeneration and supernumerary limb formation in axolotls (Ambystoma mexicanum). We show that the two tissues provide complementary cross-inductive signals that are required for limb outgrowth. A blastema composed solely of anterior tissue normally regresses rather than forming a limb, but activation of hedgehog (HH) signalling was sufficient to drive regeneration of an anterior blastema to completion owing to its ability to maintain fibroblast growth factor (FGF) expression, the key signalling activity responsible for blastema outgrowth. In blastemas composed solely of posterior tissue, HH signalling was not sufficient to drive regeneration; however, ectopic expression of FGF8 together with endogenous HH signalling was sufficient. In axolotls, FGF8 is expressed only in the anterior mesenchyme and maintenance of its expression depends on sonic hedgehog (SHH) signalling from posterior tissue. Together, our findings identify key anteriorly and posteriorly localized signals that promote limb regeneration and show that these single factors are sufficient to drive non-regenerating blastemas to complete regeneration with full elaboration of skeletal elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nacu, Eugeniu -- Gromberg, Elena -- Oliveira, Catarina R -- Drechsel, David -- Tanaka, Elly M -- England -- Nature. 2016 Apr 27;533(7603):407-10. doi: 10.1038/nature17972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DFG Research Center for Regenerative Therapies, Technische Universitat Dresden, 01307 Dresden, Germany. ; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. ; Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, 4099-003 Porto, Portugal.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120163" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    MARCKS-like protein is an initiating molecule in axolotl appendage regeneration (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-03-05
    Description: Identifying key molecules that launch regeneration has been a long-sought goal. Multiple regenerative animals show an initial wound-associated proliferative response that transits into sustained proliferation if a considerable portion of the body part has been removed. In the axolotl, appendage amputation initiates a round of wound-associated cell cycle induction followed by continued proliferation that is dependent on nerve-derived signals. A wound-associated molecule that triggers the initial proliferative response to launch regeneration has remained obscure. Here, using an expression cloning strategy followed by in vivo gain- and loss-of-function assays, we identified axolotl MARCKS-like protein (MLP) as an extracellularly released factor that induces the initial cell cycle response during axolotl appendage regeneration. The identification of a regeneration-initiating molecule opens the possibility of understanding how to elicit regeneration in other animals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795554/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795554/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sugiura, Takuji -- Wang, Heng -- Barsacchi, Rico -- Simon, Andras -- Tanaka, Elly M -- England -- Nature. 2016 Mar 10;531(7593):237-40. doi: 10.1038/nature16974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DFG Research Center for Regenerative Therapies (CRTD), Technische Universitat Dresden, Fetscherstrasse 105, 01307 Dresden, Germany. ; Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. ; Karolinska Institute, Department of Cell and Molecular Biology, Centre of Developmental Biology for Regenerative Medicine, SE-171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934225" target="_blank"〉PubMed〈/a〉
    Keywords: Ambystoma mexicanum/injuries/*physiology ; Amputation, Traumatic/metabolism ; Animals ; Cell Cycle/genetics ; Cell Proliferation/genetics ; Cloning, Molecular ; Extremities/injuries/*physiology ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism/secretion ; Membrane Proteins/genetics/*metabolism/secretion ; Mice ; Molecular Sequence Data ; Muscle Fibers, Skeletal/cytology/physiology ; Notophthalmus viridescens/genetics/injuries/physiology ; Regeneration/*physiology ; Tail/cytology/injuries/physiology ; Wound Healing/physiology ; Xenopus ; Zebrafish
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Reconstitution of the central and peripheral nervous system during salamander tail regeneration (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-07-24
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Salamander nervous system regeneration [Developmental Biology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-08-22
    Description: We show that after tail amputation in Ambystoma mexicanum (Axolotl) the correct number and spacing of dorsal root ganglia are regenerated. By transplantation of spinal cord tissue and nonclonal neurospheres, we show that the central spinal cord represents a source of peripheral nervous system cells. Interestingly, melanophores migrate from preexisting...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 10
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    Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018
    Description: 〈p〉Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. However, the molecular understanding of blastema formation had previously been hampered by the inability to identify and isolate blastema precursor cells in the adult tissue. We have used a combination of Cre-loxP reporter lineage tracking and single-cell messenger RNA sequencing (scRNA-seq) to molecularly track mature connective tissue (CT) cell heterogeneity and its transition to a limb blastema state. We have uncovered a multiphasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that recapitulates an embryonic limb bud–like phenotype including multipotency within the CT lineage. Together, our data illuminate molecular and cellular reprogramming during complex organ regeneration in a vertebrate.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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