Li J , Zhang S , Amaya E .

MR/L007525/1 Medical Research Council , MRC_MR/L007525/1 Medical Research Council

	Figure 1. Single‐cell wound responses. (A) Immediate signals, including calcium, IP4, and others, are produced in a gradient at the wound edge, upstream of the cytoskeletal signaling. (B) From 30 sec post wounding onwards, small Rho GTPases Cdc42 and RhoA are activated at the wound edge. Spatial patterning of the circumferential rings of Cdc42 and RhoA is regulated by Abr, a dual‐functional GAP/GEF, which separates active Cdc42 and active RhoA into an outer ring and an inner ring, respectively. (C) Cytoskeletal machinery in single‐cell wound closure. Myosin‐2 and F‐actin also accumulate circumferentially at the wound edge, and the closure of this actomyosin ring is driven by a centripetal gradient of RhoA activity (box). Reciprocally, this RhoA activity is also regulated by treadmilling of the actin filaments at the wound edge
	Figure 2. Stages of multicellular wound healing. (A) In an unwounded epithelium, calcium ions are stored in the network of smooth endoplasmic reticulum (ER) and cell shape is maintained by cortical actin. Blue beads, calcium ions. (B) At early stages post wounding, calcium ions are released from the ER storage through calcium channels. The opening of the calcium channels is promoted by both IP3 and the product of Itpkb, IP4. The wave of calcium release propagates planarly across several rows of epithelial cells, mobilizing a larger region of the epithelial sheet for reepithelialization. On the other hand, cortical actin in leading edge cells undergoes reorganization and forms a contractile actomyosin cable at the wound edge. Itpkb regulates the accumulation of F‐actin, whereas Erk signaling regulates myosin‐2 activation, mediated by active RhoA. PI3K activity is inhibited at this stage. (C) Closure of the wound at a later stage is driven by filopodial zippering at the leading edge. PI3K signaling is active, and through Rac and Cdc42 transforms early‐stage actomyosin cable to filopodial protrusions
	Figure 3. Stages of tadpole tail regeneration. (A) A Xenopus tadpole tail is composed of a number of axial structures including the spinal cord, notochord, and somites. An unamputated tail is in a polarized state, sustained by V‐ATPase pumps in the skin. (B) After amputation, wounded tail is depolarized and simultaneously reactive oxygen species (ROS) are produced at the amputation site. Downstream targets of the ROS include Wnt and FGF, and a number of other signaling pathways are required for successful regeneration such as Shh, TGF‐β, BMP, Notch, and Hippo pathways. V‐ATPases are also upregulated at this stage to repolarize the skin. (C) A fully functional tail is regenerated 7 days after amputation. The growth and termination of a regenerating tail are regulated by PCP signaling. BMP, bone morphogenetic protein; FGF, fibroblast growth factor; TGF‐β, transforming growth factor β; PCP, planar cell polarity
	Figure 4. Xenopus as a model to compare regenerative and non‐regenerative limbs. Before metamorphosis, Xenopus froglets are capable of regenerating amputated limbs. Listed are required genes and pathways in different processes of limb regeneration, including growth, patterning, joint and muscle development. Post‐metamorphic froglets enter a non‐permissive stage of limb regeneration when amputated limb can only grow into a spike instead of a restored limb. Many of the upregulated genes and activated pathways in the permissive stage are not properly expressed or activated at the non‐permissive stage

Amaya, Xenomics. 2005, Pubmed, Xenbase

Amaya, Xenomics. 2005, Pubmed , Xenbase
Beane, Inhibition of planar cell polarity extends neural growth during regeneration, homeostasis, and development. 2012, Pubmed , Xenbase
Beck, Temporal requirement for bone morphogenetic proteins in regeneration of the tail and limb of Xenopus tadpoles. 2006, Pubmed , Xenbase
Beck, Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate. 2003, Pubmed , Xenbase
Beck, Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms. 2009, Pubmed , Xenbase
Bedard, The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. 2007, Pubmed
Bement, Wound-induced assembly and closure of an actomyosin purse string in Xenopus oocytes. 1999, Pubmed , Xenbase
Benink, Concentric zones of active RhoA and Cdc42 around single cell wounds. 2005, Pubmed , Xenbase
Berkowitz, Magainins: a new family of membrane-active host defense peptides. 1990, Pubmed , Xenbase
Bertolotti, Skin wound healing in different aged Xenopus laevis. 2013, Pubmed , Xenbase
Brockes, Appendage regeneration in adult vertebrates and implications for regenerative medicine. 2005, Pubmed
Burkel, A Rho GTPase signal treadmill backs a contractile array. 2012, Pubmed , Xenbase
Chen, Tadpole tail regeneration in Xenopus. 2014, Pubmed , Xenbase
Chen, C/EBPalpha initiates primitive myelopoiesis in pluripotent embryonic cells. 2009, Pubmed , Xenbase
Christen, All limbs are not the same. 1998, Pubmed , Xenbase
Clark, Integration of single and multicellular wound responses. 2009, Pubmed , Xenbase
Clark, Identification of small molecule inhibitors of cytokinesis and single cell wound repair. 2012, Pubmed , Xenbase
Costa, spib is required for primitive myeloid development in Xenopus. 2008, Pubmed , Xenbase
Davidson, Embryonic wound healing by apical contraction and ingression in Xenopus laevis. 2002, Pubmed , Xenbase
DENT, Limb regeneration in larvae and metamorphosing individuals of the South African clawed toad. 1962, Pubmed
Di Grazia, The Frog Skin-Derived Antimicrobial Peptide Esculentin-1a(1-21)NH2 Promotes the Migration of Human HaCaT Keratinocytes in an EGF Receptor-Dependent Manner: A Novel Promoter of Human Skin Wound Healing? 2015, Pubmed
Filoni, Effect of denervation on hindlimb regeneration in Xenopus laevis larvae. 1990, Pubmed , Xenbase
Franchini, The thymus and skin wound healing in Xenopus laevis adults. 2014, Pubmed , Xenbase
Fuchigami, Exposure to external environment of low ion concentrations is the trigger for rapid wound closure in Xenopus laevis embryos. 2011, Pubmed , Xenbase
Fukazawa, Suppression of the immune response potentiates tadpole tail regeneration during the refractory period. 2009, Pubmed , Xenbase
Gargioli, Cell lineage tracing during Xenopus tail regeneration. 2004, Pubmed , Xenbase
Gilchrist, Defining a large set of full-length clones from a Xenopus tropicalis EST project. 2004, Pubmed , Xenbase
Godwin, Scar-free wound healing and regeneration in amphibians: immunological influences on regenerative success. 2014, Pubmed , Xenbase
Godwin, The promise of perfect adult tissue repair and regeneration in mammals: Learning from regenerative amphibians and fish. 2014, Pubmed
Gurtner, Wound repair and regeneration. 2008, Pubmed
Harland, Xenopus research: metamorphosed by genetics and genomics. 2011, Pubmed , Xenbase
Harty, Regeneration or scarring: an immunologic perspective. 2003, Pubmed
Haslam, From frog integument to human skin: dermatological perspectives from frog skin biology. 2014, Pubmed
Hayashi, Transcriptional regulators in the Hippo signaling pathway control organ growth in Xenopus tadpole tail regeneration. 2014, Pubmed , Xenbase
Hellsten, The genome of the Western clawed frog Xenopus tropicalis. 2010, Pubmed , Xenbase
Herrgen, Calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain. 2014, Pubmed , Xenbase
Ho, TGF-beta signaling is required for multiple processes during Xenopus tail regeneration. 2008, Pubmed , Xenbase
Ishibashi, Highly efficient bi-allelic mutation rates using TALENs in Xenopus tropicalis. 2012, Pubmed , Xenbase
Kawasumi, Wound healing in mammals and amphibians: toward limb regeneration in mammals. 2013, Pubmed , Xenbase
Keenan, Xenopus Limb bud morphogenesis. 2016, Pubmed , Xenbase
Kragl, Cells keep a memory of their tissue origin during axolotl limb regeneration. 2009, Pubmed
Kroll, Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation. 1996, Pubmed , Xenbase
Kumar, Nerve dependence in tissue, organ, and appendage regeneration. 2012, Pubmed , Xenbase
Lee-Liu, Genome-wide expression profile of the response to spinal cord injury in Xenopus laevis reveals extensive differences between regenerative and non-regenerative stages. 2014, Pubmed , Xenbase
Lee-Liu, Spinal cord regeneration: lessons for mammals from non-mammalian vertebrates. 2013, Pubmed
Li, ERK and phosphoinositide 3-kinase temporally coordinate different modes of actin-based motility during embryonic wound healing. 2013, Pubmed , Xenbase
Lin, Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. 2008, Pubmed , Xenbase
Lin, Imparting regenerative capacity to limbs by progenitor cell transplantation. 2013, Pubmed , Xenbase
Lipsky, Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream. 2008, Pubmed
Lo, Reversal of muscle differentiation during urodele limb regeneration. 1993, Pubmed
Love, Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration. 2013, Pubmed , Xenbase
Love, Carbohydrate metabolism during vertebrate appendage regeneration: what is its role? How is it regulated?: A postulation that regenerating vertebrate appendages facilitate glycolytic and pentose phosphate pathways to fuel macromolecule biosynthesis. 2014, Pubmed , Xenbase
Love, Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration. 2011, Pubmed , Xenbase
Love, pTransgenesis: a cross-species, modular transgenesis resource. 2011, Pubmed , Xenbase
Mandato, Xenopus egg extracts as a model system for analysis of microtubule, actin filament, and intermediate filament interactions. 2001, Pubmed , Xenbase
Mashreghi, Topical effects of frog "Rana ridibunda" skin secretions on wound healing and reduction of wound microbial load. 2013, Pubmed
McCusker, The axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods. 2015, Pubmed
McEwan, Expression of key retinoic acid modulating genes suggests active regulation during development and regeneration of the amphibian limb. 2011, Pubmed , Xenbase
McNeil, Loss, restoration, and maintenance of plasma membrane integrity. 1997, Pubmed
McNeil, Plasma membrane disruption: repair, prevention, adaptation. 2003, Pubmed
Meier, Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin. 2013, Pubmed , Xenbase
Mescher, Inflammation and immunity in organ regeneration. 2017, Pubmed , Xenbase
Miyake, Vesicle accumulation and exocytosis at sites of plasma membrane disruption. 1995, Pubmed
Mondia, Long-distance signals are required for morphogenesis of the regenerating Xenopus tadpole tail, as shown by femtosecond-laser ablation. 2011, Pubmed , Xenbase
Muneoka, Intrinsic control of regenerative loss in Xenopus laevis limbs. 1986, Pubmed , Xenbase
Muñoz, Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells. 2015, Pubmed , Xenbase
Nakayama, Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis. 2013, Pubmed , Xenbase
Paredes, Xenopus: An in vivo model for imaging the inflammatory response following injury and bacterial infection. 2015, Pubmed , Xenbase
Rinkevich, Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. 2011, Pubmed
Rodrigues, Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae. 2012, Pubmed , Xenbase
Seifert, New insights into vertebrate skin regeneration. 2014, Pubmed , Xenbase
Simon, Pattern formation of Rho GTPases in single cell wound healing. 2013, Pubmed , Xenbase
SINGER, The influence of the nerve in regeneration of the amphibian extremity. 1952, Pubmed
Slack, Cellular and molecular mechanisms of regeneration in Xenopus. 2004, Pubmed , Xenbase
Smith, XPOX2-peroxidase expression and the XLURP-1 promoter reveal the site of embryonic myeloid cell development in Xenopus. 2002, Pubmed , Xenbase
Sonnemann, Wound repair: toward understanding and integration of single-cell and multicellular wound responses. 2011, Pubmed
Soto, Inositol kinase and its product accelerate wound healing by modulating calcium levels, Rho GTPases, and F-actin assembly. 2013, Pubmed , Xenbase
Stanisstreet, Calcium and wound healing in Xenopus early embryos. 1982, Pubmed , Xenbase
Taniguchi, Spinal cord is required for proper regeneration of the tail in Xenopus tadpoles. 2008, Pubmed , Xenbase
Taniguchi, Notochord-derived hedgehog is essential for tail regeneration in Xenopus tadpole. 2014, Pubmed , Xenbase
Terasaki, Large plasma membrane disruptions are rapidly resealed by Ca2+-dependent vesicle-vesicle fusion events. 1997, Pubmed
TSCHUMI, The growth of the hindlimb bud of Xenopus laevis and its dependence upon the epidermis. 1957, Pubmed , Xenbase
Vaughan, Control of local Rho GTPase crosstalk by Abr. 2011, Pubmed , Xenbase
Vaughan, Lipid domain-dependent regulation of single-cell wound repair. 2014, Pubmed , Xenbase
Wang, Distal expression of sprouty (spry) genes during Xenopus laevis limb development and regeneration. 2014, Pubmed , Xenbase
Wood, Wound healing recapitulates morphogenesis in Drosophila embryos. 2002, Pubmed
Yokoyama, Prx-1 expression in Xenopus laevis scarless skin-wound healing and its resemblance to epimorphic regeneration. 2011, Pubmed , Xenbase
Yoshii, Wound healing ability of Xenopus laevis embryos. I. Rapid wound closure achieved by bisectional half embryos. 2005, Pubmed , Xenbase
Yu, Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. 2015, Pubmed
Zasloff, Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. 1987, Pubmed , Xenbase