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miniscule differences between sex chromosomes in the giant genome of a salamander.in the mexican axolotl (ambystoma mexicanum), sex is determined by a single mendelian factor, yet its sex chromosomes do not exhibit morphological differentiation typical of many vertebrate taxa that possess a single sex-determining locus. as sex chromosomes are theorized to differentiate rapidly, species with undifferentiated sex chromosomes provide the opportunity to reconstruct early events in sex chromosome evolution. whole genome sequencing of 48 salamanders, targeted chromosome sequencing ...201830552368
comparative transcriptomics of rat and axolotl after spinal cord injury dissects differences and similarities in inflammatory and matrix remodeling gene expression patterns.following spinal cord injury in mammals, maladaptive inflammation, and matrix deposition drive tissue scarring and permanent loss of function. in contrast, axolotls regenerate their spinal cord after severe injury fully and without scarring. to explore previously unappreciated molecules and pathways that drive tissue responses after spinal cord injury, we performed a 4-way intersection of rat and axolotl transcriptomics datasets and isolated shared genes with similar or differential expression a ...201830519154
transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution.regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. in axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue rna-sequencing. however, defining the contributions of these tissues is hindered due to limited information regarding the molecular identity of the cell types in regenerating limbs. here we report unbiased single-cell rna-sequencing on over 25,00 ...201830514844
application and optimization of crispr-cas9-mediated genome engineering in axolotl (ambystoma mexicanum).genomic manipulation is essential to the use of model organisms to understand development, regeneration and adult physiology. the axolotl (ambystoma mexicanum), a type of salamander, exhibits an unparalleled regenerative capability in a spectrum of complex tissues and organs, and therefore serves as a powerful animal model for dissecting mechanisms of regeneration. we describe here an optimized stepwise protocol to create genetically modified axolotls using the crispr-cas9 system. the protocol, ...201830429597
single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration.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) ...201830262634
using transcriptomics to enable a plethodontid salamander (bolitoglossa ramosi) for limb regeneration research.tissue regeneration is widely distributed across the tree of life. among vertebrates, salamanders possess an exceptional ability to regenerate amputated limbs and other complex structures. thus far, molecular insights about limb regeneration have come from a relatively limited number of species from two closely related salamander families. to gain a broader perspective on the molecular basis of limb regeneration and enhance the molecular toolkit of an emerging plethodontid salamander (bolitoglos ...201830253734
cell cycles during early steps of amphibian embryogenesis: a review.the published data on cell cycles during the initial (pregastrular) period of embryonic development in representatives of the class amphibia have been critically discussed. we have also used the literature data on ontogenetic diversity of these animals. the relatively small eggs of two principal model species for amphibian embryology, the mexican axolotl and the african clawed frog, undergo the extensive series of rapid synchronous cleavage divisions, after which the midblastula transition (mbt) ...201830240720
identification of axolotl bh3-only proteins and expression in axolotl organs and apoptotic limb regeneration tissue.like other urodela amphibians, axolotls are able to regenerate lost appendages, even as adults, rendering them unique among higher vertebrates. in reaction to the severe trauma of a lost limb, apoptosis seems to be primarily implicated in the removal of injured cells and tissue homeostasis. little, however, is known about apoptotic pathways and control mechanisms. therefore, here we provide additional information regarding the mechanisms of tissue degradation. expression patterns of bcl-2 family ...201830154109
[biomedical bestiary: the axolotl]. 201930125261
differences in neural stem cell identity and differentiation capacity drive divergent regenerative outcomes in lizards and salamanders.while lizards and salamanders both exhibit the ability to regenerate amputated tails, the outcomes achieved by each are markedly different. salamanders, such as ambystoma mexicanum, regenerate nearly identical copies of original tails. regenerated lizard tails, however, exhibit important morphological differences compared with originals. some of these differences concern dorsoventral patterning of regenerated skeletal and spinal cord tissues; regenerated salamander tail tissues exhibit dorsovent ...201830104374
exogenous vitamin d signaling alters skeletal patterning, differentiation, and tissue integration during limb regeneration in the axolotl.urodele amphibians such as the axolotl regenerate complete limbs as adults, and understanding how the "blueprint", or pattern, of the regenerate is established and manipulated are areas of intense interest. nutrient signaling plays an important role in pattern formation during regeneration. retinoic acid signaling is the most characterized pathway during this process. exogenous retinoic acid (ra) reprograms the pattern information in regenerating cells to a more posterior, ventral, and proximal ...201830096415
comparative transcriptomics of limb regeneration: identification of conserved expression changes among three species of ambystoma.transcriptome studies are revealing the complex gene expression basis of limb regeneration in the primary salamander model - ambystoma mexicanum (axolotl). to better understand this complexity, there is need to extend analyses to additional salamander species. using microarray and rna-seq, we performed a comparative transcriptomic study using a. mexicanum and two other ambystomatid salamanders: a. andersoni, and a. maculatum. salamanders were administered forelimb amputations and rna was isolate ...201930092345
experimentally induced metamorphosis in highly regenerative axolotl (ambystoma mexicanum) under constant diet restructures microbiota.axolotl (ambystoma mexicanum) is a critically endangered salamander species and a model organism for regenerative and developmental biology. despite life-long neoteny in nature and in captive-bred colonies, metamorphosis of these animals can be experimentally induced by administering thyroid hormones (ths). however, microbiological consequences of this experimental procedure, such as host microbiota response, remain largely unknown. here, we systematically compared host bacterial microbiota asso ...201830030457
the tmem16a channel mediates the fast polyspermy block in xenopus laevis.in externally fertilizing animals, such as sea urchins and frogs, prolonged depolarization of the egg immediately after fertilization inhibits the entry of additional sperm-a phenomenon known as the fast block to polyspermy. in the african clawed frog xenopus laevis, this depolarization is driven by ca2+-activated cl- efflux. although the prominent ca2+-activated cl- currents generated in immature x. laevis oocytes are mediated by x. laevis transmembrane protein 16a (xtmem16a) channels, little i ...201830012842
changes in the appendicular skeleton during metamorphosis in the axolotl salamander (ambystoma mexicanum).axolotl salamanders (ambystoma mexicanum) remain aquatic in their natural state, during which biomechanical forces on their diarthrodial limb joints are likely reduced relative to salamanders living on land. however, even as sexually mature adults, these amphibians can be induced to metamorphose into a weight-bearing terrestrial stage by environmental stress or the exogenous administration of thyroxine hormone. in some respects, this aquatic to terrestrial transition of axolotl salamanders throu ...201829992565
skin regeneration of amphibians: a novel model for skin regeneration as adults.adult mammals do not regenerate the dermis of the skin but form a scar after a deep skin injury. since a scar causes serious medical problems, skin regeneration, instead of formation of a scar, has been strongly desired from a clinical point of view. recent studies have suggested multiple origins of myofibroblasts, which are scar-forming cells in skin wound healing of mammals. while amphibians have skin structures that are basically common to mammals as tetrapods, both urodele and anuran amphibi ...201829947057
bapx1 upregulation is associated with ectopic mandibular cartilage development in amphibians.the emergence of novel structures during evolution is crucial for creating variation among organisms, but the underlying processes which lead to the emergence of evolutionary novelties are poorly understood. the gnathostome jaw joint is such a novelty, and the incorporation of bapx1 expression into the intermediate first pharyngeal arch may have played a major role in the evolution of this joint. knockdown experiments revealed that loss of bapx1 function leads to the loss of the jaw joint, becau ...201829942645
retinoid x receptor α downregulation is required for tail and caudal spinal cord regeneration in the adult newt.some adult vertebrate species, such as newts, axolotls and zebrafish, have the ability to regenerate their central nervous system (cns). however, the factors that establish a permissive cns environment for correct morphological and functional regeneration in these species are not well understood. recent evidence supports a role for retinoid signaling in the intrinsic ability of neurons, in these regeneration-competent species, to regrow after cns injury. previously, we demonstrated that a specif ...201829926831
an interview with elly tanaka.elly tanaka is a senior scientist at the research institute of molecular pathology in vienna, austria. her lab's research uses the axolotl - which possesses impressive regenerative capacity - to understand the molecular and cellular mechanisms underlying limb and spinal cord regeneration. we met elly in her office in vienna on the occasion of the recent sy-stem symposium (see meeting review by porrello and kirkeby in this issue) to talk about what drew her to regeneration research and the axolot ...201829884656
author correction: the axolotl genome and the evolution of key tissue formation regulators.in the originally published version of this article, the sequenced axolotl strain (the homozygous white mutant) was denoted as 'd/d' rather than 'd/d' in fig. 1a and the accompanying legend, the main text and the methods section. the original article has been corrected online.201829795340
signaling-dependent control of apical membrane size and self-renewal in rosette-stage human neuroepithelial stem cells.in the developing nervous system, neural stem cells are polarized and maintain an apical domain facing a central lumen. the presence of apical membrane is thought to have a profound influence on maintaining the stem cell state. with the onset of neurogenesis, cells lose their polarization, and the concomitant loss of the apical domain coincides with a loss of the stem cell identity. little is known about the molecular signals controlling apical membrane size. here, we use two neuroepithelial cel ...201829779899
forever young: endocrinology of paedomorphosis in the mexican axolotl (ambystoma mexicanum).the mexican axolotl (ambystoma mexicanum) is a salamander species that does not undergo metamorphosis, resulting in the retention of juvenile characteristics in the mature breeding stage (paedomorphosis). here we review the endocrinological studies investigating the proximate cause of axolotl paedomorphosis with a focus on the hypothalamo-pituitary-thyroid (hpt) axis. it is well established that axolotl paedomorphosis is a consequence of low activity of the hpt axis. the pituitary hormone thyrot ...201829777689
cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy.inducing stable control of tumour growth by tumour reversion is an alternative approach to cancer treatment when eradication of the disease cannot be achieved. the process requires re-establishment of normal control mechanisms that are lost in cancer cells so that abnormal proliferation can be halted. embryonic environments can reset cellular programmes and we previously showed that axolotl oocyte extracts can reprogram breast cancer cells and reverse their tumorigenicity. in this study, we anal ...201829662623
publisher correction: virtual genome walking across the 32 gb ambystoma mexicanum genome; assembling gene models and intronic sequence.a correction to this article has been published and is linked from the html and pdf versions of this paper. the error has been fixed in the paper.201829654245
positive in vitro wound healing effects of functional inclusion bodies of a lipoxygenase from the mexican axolotl.ambloxe is a lipoxygenase, which is up-regulated during limb-redevelopment in the mexican axolotl, ambystoma mexicanum, an animal with remarkable regeneration capacity. previous studies have shown that mammalian cells transformed with the gene of this epidermal lipoxygenase display faster migration and wound closure rate during in vitro wound healing experiments.201829626934
noncanonical hox, etv4, and gli3 gene activities give insight into unique limb patterning in salamanders.limb development in salamanders is unique among tetrapods in significant ways. not only can salamanders regenerate lost limbs repeatedly and throughout their lives, but also the preaxial zeugopodial element and digits form before the postaxial ones and, hence, with a reversed polarity compared to all other tetrapods. moreover, in salamanders with free-swimming larval stages, as exemplified by the axolotl (ambystoma mexicanum), each digit buds independently, instead of undergoing a paddle stage. ...201829602205
non-invasive cell tracking of spio labeled cells in an intrinsic regenerative environment: the axolotl limb.non-invasive methods to track the progress of stem cell therapies are important in the development of future regenerative therapies. super-paramagnetic iron oxide particles (spios) have previously been applied to track cells using magnetic resonance imaging (mri) in vivo in non-regenerative animal models. to the best of the author's knowledge, the present study investigated for the first time, the feasibility of tracking spio labeled cells in an intrinsic regenerative environment, the regenerati ...201829545849
musashi and plasticity of xenopus and axolotl spinal cord ependymal cells.the differentiated state of spinal cord ependymal cells in regeneration-competent amphibians varies between a constitutively active state in what is essentially a developing organism, the tadpole of the frog xenopus laevis, and a quiescent, activatable state in a slowly growing adult salamander ambystoma mexicanum, the axolotl. ependymal cells are epithelial in intact spinal cord of all vertebrates. after transection, body region ependymal epithelium in both xenopus and the axolotl disorganizes ...201829535610
morphological and transcriptomic analyses reveal three discrete primary stages of postembryonic development in the common fire salamander, salamandra salamandra.the postembryonic development of amphibians has been characterized as divided into three predominant periods, hereafter named primary developmental stages: premetamorphosis (prem), prometamorphosis (prom), metamorphic climax (meta), and completion of metamorphosis (postm), largely based on examination of anuran development. here, we categorized the postembryonic development of larvae of a poisonous fire salamander (salamandra salamandra) by integrating morphology and gene expression (transcripto ...201829504232
buoyancy disorders in pet axolotls ambystoma mexicanum: three cases.as far as we are aware, there are no previous reports on the pathologic conditions of buoyancy disorders in ambystoma mexicanum. herein, we describe various clinical test results, clinical outcomes, and the pathological findings of an experimental pneumonectomy procedure in 3 a. mexicanum exhibiting abnormal buoyancy. the 3 pet a. mexicanum were adults, and their respective ages and body weights were 1, 5, and 6 yr and 48, 55, and 56 g. two of these cases were confirmed via radiographic examinat ...201829384486
the axolotl genome and the evolution of key tissue formation regulators.salamanders serve as important tetrapod models for developmental, regeneration and evolutionary studies. an extensive molecular toolkit makes the mexican axolotl (ambystoma mexicanum) a key representative salamander for molecular investigations. here we report the sequencing and assembly of the 32-gigabase-pair axolotl genome using an approach that combined long-read sequencing, optical mapping and development of a new genome assembler (marvel). we observed a size expansion of introns and interg ...201829364872
biology's beloved amphibian - the axolotl - is racing towards extinction. 201732080554
evaluation of the anesthetic effects of ms222 in the adult mexican axolotl (ambystoma mexicanum).the mexican axolotl (ambystoma mexicanum) is a unique research model in several fields of medicine, where surgical and invasive procedures may be required. as yet, little is known about the efficacy of ms222 (tricaine methanesulfonate), which is the most commonly used anesthetic agent in amphibians. the main objectives of this study were to evaluate the anesthetic effects and physiological changes in adult axolotls following a 20-minute immersion bath, containing progressive ms222 concentrations ...201630050832
a tale of two axolotls.the mexican axolotl (ambystoma mexicanum) is an icon of culture, a revered aquarium pet, and a highly valued animal model in biomedical research. unfortunately, mexican axolotls are critically endangered in their natural xochimilco habitat in mexico city. if axolotls go extinct, current efforts to conserve the xochimilico ecosystem will be undermined, as will efforts to genetically manage the laboratory populations that are needed to sustain research efforts around the world. a concerted global ...201532123398
induction of metamorphosis causes differences in sex-specific allocation patterns in axolotls (ambystoma mexicanum) that have different growth histories.we tested the hypothesis that salamanders growing at different rates would have allocation patterns that differ among male and female metamorphic and larval salamanders. we raised individual axolotls, ambystoma mexicanum, on four food regimes: constant high growth (throughout the experiment), constant low growth (restricted throughout the experiment), high growth switched to low growth (ad libitum switched after 140 d to restricted), and low growth switched to high growth (restricted switched af ...201529755160
variable manifestations in the short toes (s) mutation of the axolotl.we describe a detailed histological analysis of the affected organs in the short toes (s) mutation of the mexican axolotl, ambystoma mexicanum. the s mutant animals displayed a variation in the response to the mutation such as the time of death and the degree of abnormalities of the affected organs (limbs, kidney, ducts, and reproductive structures). in addition to the numerous histological abnormalities characterized here, we also examined the presence of laminin-related molecules in s mutant k ...199329865473
the vascular structure of the kidney of the neotenous axolotl and its metamorphosed counterpart.the renal vascular and glomerular structures of the kidney of neotenous and experimentally metamorphosed axolotls (ambystoma mexicanum: amphibia, urodela) are investigated using light, transmission electron, and scanning electron microscopy of critical-point dried specimens and vascular corrosion casts. the blood vascular system of the kidney in the axolotl is generally similar to that in other urodeles. the glomeruli are comparatively large and distincly ovoid (mean size 267 × 201 μm). glomerul ...199229865583
brain-capillary architecture of the newt, triturus cristatus carnifex (caudata: salamandridae): scanning electron-microscopical study of vascular corrosion casts.the brain-microvascular architecture of the newt (triturus cristatus carnifex) was studied by scanning electron-microscopical examination of microvascular corrosion casts. it is characterized at the leptomeningeal level by a superficial network of single vessels that leave the meningeal sheath to form hairpin-shaped capillary loops. these loops penetrate the nervous parenchyma to varying depths and are variously bent, inclined, and twisted. each hairpin-like loop consists of descending and ascen ...199129865580
lateral-line neuromast development in ambystoma mexicanum and a comparison with rana pipiens.we have examined the embryonic development of the major neuromast lines of the lateral-line system in the urodele ambystoma mexicanum both in vivo (using microsurgical techniques to transplant placodes) and in preserved embryos using scanning electron microscopy (sem). we have compared this to sem observations of embryos of the anuran rana pipiens. we have determined the approximate locations of the lateral-line placodes in a. mexicanum and the approximate timing of both the migration of the lat ...198829879797
formation of the pronephros and pronephric duct rudiment in the mexican axolotl.in the mexican axolotl (ambystoma mexicanum), the pronephros begins to form at the four-somite stage. it is initially continuous with the posterior-lateral region of somite 2 and the lateral margin of somites 3 and 4. by the seven-somite stage, the pronephros has become compacted, and the cells are now morphologically distinct from the somitic cells. at this stage, a mass of loosely connected cells, apparently originating from the lateral mesoderm, is seen below somites 4 and 5. by the eight-som ...198529976020
the serotonergic somatosensory projection to the tectum of normal and eyeless salamanders.the spinotectal somatosensory projection was compared in normal, genetically eyeless, and embryonically manipulated salamanders. in normal animals, serotonin fluorescence was restricted to the intermediate tectalneuropil. this same region showed both high levels of serotonin uptake and somatosensory single unit electrical activity. in mutant eyeless salamanders and in normal animals enucleated early in development, serotonin fluorescence, serotonin uptake, and somatosensory activity were present ...198130153710
[autoradiography study of 14co2 incorporation in axolotl gastrulas]. 195813539274
action of malononitrile on the embryonic development of ambystoma mexicanum and rana temporaria. 195513267234
on the influence of neurohypophysial elements on the sodium metabolism in axolotl. 194720262722
on the structure of the insegmented egg of axolotl and the origin of morphogenic prodromes. 194620292305
centrifugal fibers in the optic nerve of the axolotl. 194521013407
differentiation of neuroblasts in the cavity of the nerve tube of axolotl larvae; tropisms of their fibers. 194521013406
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