In this Primer, we cover the evolutionary context in which salamanders emerged. Watch Queue Queue. 5). Regeneration of ocular tissues. The extinct species are grouped under Caudata and the extant ones are grouped as Urodela. The cells then start dividing to form the missing tissue. (Bottom) Studies on red-spotted newts have showed that dopaminergic and cholinergic (not shown) neurons regenerate in several brain regions after the selective ablation of individual neuronal subtypes. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-β).” – “Our results also demonstrate the presence of multiple components of the TGF-β signaling machinery in axolotl (salamander) cells. I thought I would look a bit into how these animals go about doing that and the implications for human limb regeneration. We describe a multipotent Pax7+ satellite cell population located within the skeletal muscle of the salamander limb. Importantly, these articles also give examples of how the study of these models has increased our understanding of regenerative mechanisms more broadly, and how some of the open questions in the field of regeneration may be answered using these organisms. The regeneration of appendages proceeds by local formation of a growth zone or blastema at the plane of amputation--a mechanism shared by most of the examples shown in Fig. also described the heterogeneity of wound epidermis cells during axolotl limb homeostasis and regeneration, and identified markers for ionocytes, Langerhans cells, apical, intermediate and basal epidermis and small secretory cells. Distinct roles for Pax7 and Pax3 in adult regenerative myogenesis, Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate, Comparison of molecular and cellular events during lower jaw regeneration of newt (Cynops pyrrhogaster) and West African clawed frog (Xenopus tropicalis), Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution, A de novo assembly of the newt transcriptome combined with proteomic validation identifies new protein families expressed during tissue regeneration, Deadenylation of maternal mRNAs mediated by miR-427 in Xenopus laevis embryos, A comparative perspective on brain regeneration in amphibians and teleost fish, Proliferation zones in the axolotl brain and regeneration of the telencephalon, Newly-formed neurons in the regenerating optic tectum of Triturus cristatus carnifex, Cellular contribution from dermis and cartilage to the regenerating limb blastema in axolotls, FGF8 and SHH substitute for anterior-posterior tissue interactions to induce limb regeneration, A transcriptome for the study of early processes of retinal regeneration in the adult newt, Cynops pyrrhogaster, The axolotl genome and the evolution of key tissue formation regulators, Regeneration of retinotectal projections after optic tectum removal in adult newts, Midbrain dopaminergic neurogenesis and behavioural recovery in a salamander lesion-induced regeneration model, Fundamental differences in dedifferentiation and stem cell recruitment during skeletal muscle regeneration in two salamander species, FGF and BMP derived from dorsal root ganglia regulate blastema induction in limb regeneration in Ambystoma mexicanum, Hedgehog and Wnt coordinate signaling in myogenic progenitors and regulate limb regeneration, A chromosome-scale assembly of the axolotl genome, Plasticity for axolotl lens regeneration is associated with age-related changes in gene expression, Heart regeneration in the Mexican cavefish, Hellbender genome sequences shed light on genomic expansion at the base of crown salamanders, Regeneration: Thomas Hunt Morgan's window into development. It will be interesting to determine whether this expansion and post-injury expression is a general feature of salamanders, restricted to newts or possibly only to Pleurodeles. Tadpoles, newts and other amphibian species can regenerate limbs and fish caudal fins can regenerate after amputation(ref). Loss-of-function experiments in axolotls, using TALEN and CRISPR/Cas9 genome editing, indicate that the paralogue Pax7 takes on the role that Pax3 performs in other vertebrates, as Pax7 axolotl mutants have major developmental abnormalities and lack limb muscle (Nowoshilow et al., 2018). Salamander, any member of a group of about 740 species of amphibians that have tails and that constitute the order Caudata. As such, salamanders have provided key insights into the mechanisms by which cells, tissues and organs sense and regenerate missing or damaged parts. Both established and emerging species are shown, highlighting regenerative organs/tissues and major resources available for each species. Salamanders do not offer such an approach to discovering molecular mechanisms, and this perhaps contributed to their transient decline as a research model. In contrast, the axolotl does not exhibit muscle dedifferentiation during limb regeneration; instead, new muscle fibres seem to be entirely derived from the activation of a resident Pax7-expressing stem cell population (Fei et al., 2017; Sandoval-Guzmán et al., 2014; Wang and Simon, 2016). The cells also retain positional memory during the regeneration event, allowing them to undergo the appropriate patterning to re-from an intact limb. Recently, substantial efforts have been made to establish a newt model species that is amenable to genetic manipulations on par with the axolotl. Genetically modified lines are difficult to establish due to its long generation time and complex life cycle (Abdullayev et al., 2013; Looso et al., 2013). However, it is important to remember that immune cells infiltrate the axolotl regenerating limb and that macrophages are necessary for blastema formation (Godwin et al., 2013). How and by which cells FGF and Hedgehog signalling are translated into positional values during limb regeneration remains uncertain (Bryant and Gardiner, 2018). 1). We apologize to the authors whose work we could not cite due to limitations in the number of references. Each article provides background information about the phylogenetic position of the species, its life-cycle and habitat, the different organs and tissues that regenerate, and the experimental tools and techniques that are available for studying these organisms in a regenerative context. Salamanders and many other related amphibians have a remarkable aptitude for the regeneration of various body structures when compared to other vertebrates. My Thoughts on How to Live My Longest Healthy Life (Healthspan). It is possible that the relative levels of gene expression in neighbouring cells contribute to positional values. The best staging, based on meticulous histological series, is available for Notophthalmus, which completes adult limb regeneration within less than 2 months (Iten and Bryant, 1973) (Fig. osti.gov journal article: regeneration of locally irradiated salamander limbs following superficial skin incisions or nerve transection. In other words, an amputation through the upper arm will lead to regeneration of a limb from elbow to hand, while an amputation through the lower arm will not regenerate a second upper elbow but only the more-distal structures (the wrist and hand). But not all animals use the pluripotent cells for regeneration. In the second phase of limb regeneration, referred to as the redevelopment phase, blastema cells stop proliferating and start to redifferentiate to regenerate the lost part [1], [8](ref).”. After the completion of wound healing, the basal epidermis also expresses agr2a. 4), pigment cells are the principal source of a new lens: in this case, also referred to as Wolffian regeneration, fully differentiated pigmented epithelial cells dedifferentiate and proliferate, but only the cells that originated from the dorsal iris transdifferentiate into a new lens (Eguchi et al., 2011). Salamander genomes are vast, ranging between 14 and 120 Gb (Brockes, 2015), and their sheer size has delayed their characterization. This is followed by the formation of neuro-retinal cell types in an order that recapitulates development: ganglion cells form first, followed by amacrine cells, horizontal cells and Müller glia. Indeed, it may be possible that larval animals are more prone to reactivate developmental programs than post-metamorphic adults.

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