Publications

surface contraction waves or cell proliferation waves in the presumptive neurectoderm during amphibian gastrulation: mexican axolotl versus african clawed frog.	this essay represents a critical analysis of the literary data on various types of waves occurring in the amphibian embryos during gastrulation. a surface contraction wave travels through the presumptive neurectoderm during mexican axolotl gastrulation. this wave coincides temporally and spatially with involution of the inducing chordomesoderm and with the prospective neural plate. by contrast, there is no similar surface contraction wave during african clawed frog gastrulation. however, the cla ...	2020	33181236
the first report on circulating micrornas at pre- and post-metamorphic stages of axolotls.	micrornas (mirnas) are endogenously coded small rnas, implicated in post-transcriptional gene regulation by targeting messenger rnas (mrnas). circulating mirnas are cell-free molecules, found in body fluids, such as blood and saliva, and emerged recently as potential diagnostic biomarkers. functions of circulating mirnas and their roles in target tissues have been extensively investigated in mammals, and the reports on circulating mirnas in non-mammalian clades are largely missing. salamanders d ...	2020	33131713
conservation analysis of core cell cycle regulators and their transcriptional behavior during limb regeneration in ambystoma mexicanum.	ambystoma mexicanum (axolotl) has been one of the major experimental models for the study of regeneration during the past 100 years. axolotl limb regeneration takes place through a multi-stage and complex developmental process called epimorphosis that involves diverse events of cell reprogramming. such events start with dedifferentiation of somatic cells and the proliferation of quiescent stem cells to generate a population of proliferative cells called blastema. once the blastema reaches a matu ...	2020	33127453
single-cell rna-seq reveals novel mitochondria-related musculoskeletal cell populations during adult axolotl limb regeneration process.	while the capacity to regenerate tissues or limbs is limited in mammals, including humans, axolotls are able to regrow entire limbs and major organs after incurring a wound. the wound blastema has been extensively studied in limb regeneration. however, due to the inadequate characterization of ecm and cell subpopulations involved in the regeneration process, the discovery of the key drivers for human limb regeneration remains unknown. in this study, we applied large-scale single-cell rna sequenc ...	2020	33116295
salamander-eci: an optical clearing protocol for the three-dimensional exploration of regeneration.	salamander limb regeneration is a complex biological process that entails the orchestration of multiple cellular and molecular mechanisms in a three-dimensional space. hence, a comprehensive understanding of this process requires whole-structure level explorations. recent advances in imaging and optical clearing methods have transformed the study of regenerative phenomena, allowing the three-dimensional visualization of structures and entire organisms.	2020	33084146
axolotl liver regeneration is accomplished via compensatory congestion mechanisms regulated by erk signaling after partial hepatectomy.	axolotls have remarkable organ-level regeneration capability. they can regenerate their limbs, tail, brain, gills, and heart. the liver had been considered to be a regenerative organ in these highly regeneration-competent animals. therefore, no research had been performed on liver regeneration in urodele amphibians. in the present study, we focused on axolotl liver regeneration and found a unique regeneration mechanism compared with other vertebrates.	2020	33064366
3d visualization of macromolecule synthesis.	measuring nascent macromolecular synthesis in vivo is key to understanding how cells and tissues progress through development and respond to external cues. here, we perform in vivo injection of alkyne- or azide-modified analogs of thymidine, uridine, methionine, and glucosamine to label nascent synthesis of dna, rna, protein, and glycosylation. three-dimensional volumetric imaging of nascent macromolecule synthesis was performed in axolotl salamander tissue using whole mount click chemistry-base ...	2020	33051003
mandibular musculature constrains brain-endocast disparity between sarcopterygians.	the transition from water to land by the earliest tetrapods in the devonian period is seen as one of the greatest steps in evolution. however, little is understood concerning changes in brain morphology over this transition. here, we determine the brain-braincase relationship in fishes and basal lissamphibians as a proxy to elucidate the changes that occurred over the fish-tetrapod transition. we investigate six basal extant sarcopterygians spanning coelacanths to salamanders (latimeria chalumna ...	2020	33047053
a comparative perspective on lung and gill regeneration.	the ability to continuously grow and regenerate the gills throughout life is a remarkable property of fish and amphibians. considering that gill regeneration was first described over one century ago, it is surprising that the underlying mechanisms of cell and tissue replacement in the gills remain poorly understood. by contrast, the mammalian lung is a largely quiescent organ in adults but is capable of facultative regeneration following injury. in the course of the past decade, it has been reco ...	2020	33037099
large-scale variation in snp density within the laboratory axolotl (ambystoma mexicanum).	recent efforts to assemble and analyze the ambystoma mexicanum genome have dramatically improved the potential to develop molecular tools and pursue genome-wide analyses of genetic variation.	2020	33001517
divergent influenza-like viruses of amphibians and fish support an ancient evolutionary association.	influenza viruses (family orthomyxoviridae) infect a variety of vertebrates, including birds, humans, and other mammals. recent metatranscriptomic studies have uncovered divergent influenza viruses in amphibians, fish and jawless vertebrates, suggesting that these viruses may be widely distributed. we sought to identify additional vertebrate influenza-like viruses through the analysis of publicly available rna sequencing data. accordingly, by data mining, we identified the complete coding segmen ...	2020	32962015
limb regeneration in salamanders: the plethodontid tale.	salamanders are the only vertebrates that can regenerate limbs as adults. this makes them ideal models to investigate cellular and molecular mechanisms of tissue regeneration. ambystoma mexicanum and nothopthalmus viridescens have long served as primary salamander models of limb regeneration, and the recent sequencing of the axolotl genome now provides a blueprint to mine regeneration insights from other salamander species. in particular, there is a need to study south american plethodontid sala ...	2020	32930368
author correction: label-free imaging of tissue architecture during axolotl peripheral nerve regeneration in comparison to functional recovery.	an amendment to this paper has been published and can be accessed via a link at the top of the paper.	2020	32929166
immunity in salamander regeneration: where are we standing and where are we headed?	salamanders exhibit the most extensive regenerative repertoire among vertebrates, being able to accomplish scar-free healing and faithful regeneration of significant parts of the eye, heart, brain, spinal cord, jaws and gills, as well as entire appendages throughout life. the cellular and molecular mechanisms underlying salamander regeneration are currently under extensive examination, with the hope of identifying the key drivers in each context, understanding interspecies differences in regener ...	2020	32924213
intrinsic heart regeneration in adult vertebrates may be strictly limited to low-metabolic ectotherms.	the heart has a high-metabolic rate, and its "around-the-clock" vital role to sustain life sets it apart in a regenerative setting from other organs and appendages. the landscape of vertebrate species known to perform intrinsic heart regeneration is strongly biased toward ectotherms-for example, fish, salamanders, and embryonic/neonatal ectothermic mammals. it is hypothesized that intrinsic heart regeneration is exclusively limited to the low-metabolic hearts of ectotherms. the biomedical field ...	2020	32914411
axolotl ambystoma mexicanum extract induces cell cycle arrest and differentiation in human acute myeloid leukemia hl-60 cells.	acute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve patient outcome and minimize toxicity is needed. in this study, the antitumor activity of axolotl (axo) ambystoma mexicanum crude extract was assessed in vitro on the human acute myeloid leukemia hl-60 c ...	2020	32873193
the rax homeobox gene is mutated in the eyeless axolotl, ambystoma mexicanum.	vertebrate eye formation requires coordinated inductive interactions between different embryonic tissue layers, first described in amphibians. a network of transcription factors and signaling molecules controls these steps, with mutations causing severe ocular, neuronal, and craniofacial defects. in eyeless mutant axolotls, eye morphogenesis arrests at the optic vesicle stage, before lens induction, and development of ventral forebrain structures is disrupted.	2020	32864847
an aryl hydrocarbon receptor from the caecilian gymnopis multiplicata suggests low dioxin affinity in the ancestor of all three amphibian orders.	the aryl hydrocarbon receptor (ahr) plays pleiotropic roles in the development and physiology of vertebrates in conjunction with xenobiotic and endogenous ligands. it is best known for mediating the toxic effects of dioxin-like pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd). while most vertebrates possess at least one ahr that binds tcdd tightly, amphibian ahrs bind tcdd with very low affinity. previous analyses of ahrs from xenopus laevis (a frog; order anura) and ambystoma mexic ...	2020	32858041
immunochemical detection of modified cytosine species in lampbrush chromatin.	the lampbrush chromosomes found in the giant nucleus or germinal vesicle (gv) of amphibian oocytes provide unique opportunities for discrete closed and open chromatin structural domains to be directly observable by simple light microscopy. moreover, the method described here for preparing spreads of lampbrush chromatin for immunostaining enables a straightforward approach to establishing the distributions of modified nucleotides within and between structurally and functionally distinctive chroma ...	2021	32822030
transcriptome dataset for rna-seq analysis of axolotl embryonic oropharyngeal endoderm explants.	animal nutrition and toxin deterrence rely on the ability to taste, which occurs through columnar taste cells clustered within taste buds. taste buds in mammals are located within specialized tissues, called papillae. however, taste buds in fish and amphibians, such as axolotls (ambystoma mexicanum), are not housed in papillae, rather they are embedded within the pharyngeal epithelium. this simplified tissue level organization, along with the ability of cultured oropharyngeal explants from early ...	2020	32802925
dynamic cell transition and immune response landscapes of axolotl limb regeneration revealed by single-cell analysis.		2020	32748350
bmp signaling is essential for sustaining proximo-distal progression in regenerating axolotl limbs.	amputation of a salamander limb triggers a regeneration process that is perfect. a limited number of genes have been studied in this context and even fewer have been analyzed functionally. in this work, we use the bmp signaling inhibitor ldn193189 on ambystoma mexicanum to explore the role of bmps in regeneration. we find that bmp signaling is required for proper expression of various patterning genes and that its inhibition causes major defects in the regenerated limbs. fgf8 is downregulated wh ...	2020	32665245
inhibition of wound epidermis formation via full skin flap surgery during axolotl limb regeneration.	classical experiments in salamander regenerative biology over the last century have long established that the wound epidermis is a crucial signaling structure that forms rapidly post-amputation and is required for limb regeneration. however, methods to study its precise function at the molecular level over the last decades have been limited due to a paucity of precise functional techniques and genomic information available in salamander model systems. excitingly, the recent plethora of sequencin ...	2020	32658179
exploring the role of micrornas in axolotl regeneration.	the axolotl, ambystoma mexicanum, is used extensively for research in developmental biology, particularly for its ability to regenerate and restore lost organs, including in the nervous system, to full functionality. regeneration in mammals typically depends on the healing process and scar formation with limited replacement of lost tissue. other organisms, such as spiny mice (acomys cahirinus), salamanders, and zebrafish, are able to regenerate some damaged body components. blastema is a tissue ...	2020	32638401
identification of immune and non-immune cells in regenerating axolotl limbs by single-cell sequencing.	immune cells are known to be critical for successful limb regeneration in the axolotl (ambystoma mexicanum), but many details regarding their identity, behavior, and function are yet to be resolved. we isolated peripheral leukocytes from the blood of adult axolotls and then created two samples for single-cell sequencing: 1) peripheral leukocytes (n = 7889) and 2) peripheral leukocytes with presumptive macrophages from the intraperitoneal cavity (n = 4998). using k-means clustering, we identified ...	2020	32562784
introducing www.axolotl-omics.org - an integrated -omics data portal for the axolotl research community.	genomic resources are indispensable for biological investigations in model organisms. in recent years, a number of genomic resources including a full genome assembly, extensive transcriptomic data, as well as genome editing has been developed for the axolotl, a classical model organism for developmental, neurobiological and regeneration studies, making the axolotl a highly versatile system. here we describe the axolotl-omics website that allows rapid ortholog searches, and access to genome and t ...	2020	32540400
a versatile depigmentation, clearing, and labeling method for exploring nervous system diversity.	tissue clearing combined with deep imaging has emerged as a powerful alternative to classical histological techniques. whereas current techniques have been optimized for imaging selected nonpigmented organs such as the mammalian brain, natural pigmentation remains challenging for most other biological specimens of larger volume. we have developed a fast depigmentation-plus-clearing method (deep-clear) that is easily incorporated in existing workflows and combines whole system labeling with a spe ...	2020	32523996
neural regulation in tooth regeneration of ambystoma mexicanum.	the presence of nerves is an important factor in successful organ regeneration in amphibians. the mexican salamander, ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. however, the nerve-dependency of tooth regeneration has not been evaluated. here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called combi and found that tooth regeneration is nerve-dependent although the dentary bone is independen ...	2020	32518359
preclinical molecular signatures of spinal cord functional restoration: optimizing the metamorphic axolotl (ambystoma mexicanum) model in regenerative medicine.	regenerative medicine offers hope for patients with diseases of the central and peripheral nervous system. urodele amphibians such as axolotl display an exceptional regenerative capacity and are considered as essential preclinical model organisms in neurology and regenerative medicine research. earlier studies have suggested that the limb regeneration ability of this salamander notably decreases with induction of metamorphosis by thyroid hormones. metamorphic axolotl requires further validation ...	2020	32496969
elastic recoil action amplifies jaw closing speed in an aquatic feeding salamander.	tendon springs often influence locomotion by amplifying the speed and power of limb joint rotation. however, less is known about elastic recoil action in feeding systems, particularly for small aquatic animals. here, we ask if elastic recoil amplifies the speed of gape closing during aquatic food processing in the axolotl (ambystoma mexicanum). we measure activation of the adductor mandibulae externus via electromyography and strain of the jaw adductor muscle-tendon unit (mtu), and gape kinemati ...	2020	32429804
a histological study of normal and pathological limb regeneration in the mexican axolotl ambystoma mexicanum.	salamanders show unparalleled capacities of tissue regeneration amongst tetrapods (four-legged vertebrates), being able to repair and renew lost or damage body parts, such as tails, jaws, and limbs in a seemingly perfect fashion. despite countless studies on axolotl (ambystoma mexicanum) regeneration, only a few studies have thus far compared gross morphological and histological features of the original and regenerated limb skeleton. therein, most studies have focused on nerves or muscles, while ...	2020	32394624
what the salamander eye has been telling the vision scientist's brain.	salamanders have been habitual residents of research laboratories for more than a century, and their history in science is tightly interwoven with vision research. nevertheless, many vision scientists - even those working with salamanders - may be unaware of how much our knowledge about vision, and particularly the retina, has been shaped by studying salamanders. in this review, we take a tour through the salamander history in vision science, highlighting the main contributions of salamanders to ...	2020	32359891
ra signaling in limb development and regeneration in different species.	this chapter brings together data on the role of retinoic acid (ra) in the embryonic development of fins in zebrafish , limbs in amphibians , chicks , and mice, and regeneration of the amphibian limb . the intention is to determine whether there is a common set of principles by which we can understand the mode of action of ra in both embryos and adults. what emerges from this synthesis is that there are indeed commonalities in the involvement of ra in processes that ventralize, posteriorize, and ...	2020	32297297
purification of soluble membrane-bound ambystoma mexicanum epidermal lipoxygenase from e. coli and its growth effect on human fetal foreskin fibroblast.	lipoxygenases are non-heme iron-containing lipid dioxygenases enzymes that catalyze the hydroperoxidation of lipids. the mexican axolotl (ambystoma mexicanum) is a prominent source of the enzyme with a regeneration capacity in limbs. it has been shown that transfected human osteosarcoma and keratinocyte cells with epidermal lipoxygenase (loxe) have an increased rate of cell migration. in the present study, loxe, a peripheral membrane protein, was produced in escherichia coli. the enzyme was puri ...	2020	32285244
dissecting the molecular signature of spinal cord regeneration in the axolotl model.	thousands of people are affected by central nervous system (cns) dysfunctions each year, with stroke and spinal cord injury (sci) being the most frequent causes. although there is some evidence of partial cns self-repair (via migration of neural stem cells to the injury zone and adult neurogenesis), due to restricted regeneration capacity in mammals, acute or chronic spinal cord injuries cannot be repaired completely. therefore, to expand the availability of treatment options for sci, research o ...	2020	32211250
small circrnas with self-cleaving ribozymes are highly expressed in diverse metazoan transcriptomes.	ribozymes are catalytic rnas present in modern genomes but regarded as remnants of a prebiotic rna world. the paradigmatic hammerhead ribozyme (hhr) is a small self-cleaving motif widespread from bacterial to human genomes. here, we report that most of the classical type i hhrs frequently found in the genomes of animals are contained within a novel family of non-autonomous non-ltr retrotransposons of the retrozyme class. these retroelements are expressed as abundant linear and circular rnas of ∼ ...	2020	32198887
von willebrand factor d and egf domains is an evolutionarily conserved and required feature of blastemas capable of multitissue appendage regeneration.	regenerative ability varies tremendously across species. a common feature of regeneration of appendages such as limbs, fins, antlers, and tails is the formation of a blastema-a transient structure that houses a pool of progenitor cells that can regenerate the missing tissue. we have identified the expression of von willebrand factor d and egf domains (vwde) as a common feature of blastemas capable of regenerating limbs and fins in a variety of highly regenerative species, including axolotl (amby ...	2020	32163674
eya2 promotes cell cycle progression by regulating dna damage response during vertebrate limb regeneration.	how salamanders accomplish progenitor cell proliferation while faithfully maintaining genomic integrity and regenerative potential remains elusive. here we found an innate dna damage response mechanism that is evident during blastema proliferation (early- to late-bud) and studied its role during tissue regeneration by ablating the function of one of its components, eyes absent 2. in eya2 mutant axolotls, we found that dna damage signaling through the h2ax histone variant was deregulated, especia ...	2020	32142407
timemeter assesses temporal gene expression similarity and identifies differentially progressing genes.	comparative time series transcriptome analysis is a powerful tool to study development, evolution, aging, disease progression and cancer prognosis. we develop timemeter, a statistical method and tool to assess temporal gene expression similarity, and identify differentially progressing genes where one pattern is more temporally advanced than the other. we apply timemeter to several datasets, and show that timemeter is capable of characterizing complicated temporal gene expression associations. i ...	2020	32123905
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 ...	2015	32123398
multi-glomerular projection of single olfactory receptor neurons is conserved among amphibians.	individual receptor neurons in the peripheral olfactory organ extend long axons into the olfactory bulb forming synapses with projection neurons in spherical neuropil regions, called glomeruli. generally, odor map formation and odor processing in all vertebrates is based on the assumption that receptor neuron axons exclusively connect to a single glomerulus without any axonal branching. we comparatively tested this hypothesis in multiple fish and amphibian species (both sexes) by applying sparse ...	2020	32080843
biology's beloved amphibian - the axolotl - is racing towards extinction.		2017	32080554
generation of chimeric axolotls with mutant haploid limbs through embryonic grafting.	a growing set of genetic techniques and resources enable researchers to probe the molecular origins of the ability of some species of salamanders, such as axolotls, to regenerate entire limbs as adults. here, we outline techniques used to generate chimeric axolotls with cas9-mutagenized haploid forelimbs that can be used for exploring gene function and the fidelity of limb regeneration. we combine several embryological and genetic techniques, including haploid generation via in vitro activation, ...	2020	32065121
proteome data to explore the axolotl limb regeneration capacity at neotenic and metamorphic stages.	the presented data article reports protein expression profiles during a time course of limb regeneration in the highly regenerative neotenic and regeneration-deficient metamorphic axolotl (ambystoma mexicanum). a protein database was first generated from transcriptome data, which was used concomitantly with nanolc-ms/ms to identify and assess significant changes of protein levels among 0, 1, 4, and 7 days post-amputation (dpa) in both animal stages, yielding a total of 714 significant differenti ...	2020	32055664
transcriptome analysis of axolotl oropharyngeal explants during taste bud differentiation stages.	the mexican salamander, ambystoma mexicanum (axolotl), is an excellent vertebrate model system to understand development and regeneration. studies in axolotl embryos have provided important insights into taste bud development. taste bud specification and determination occur in the oropharyngeal endoderm of axolotl embryos during gastrulation and neurulation, respectively, whereas taste bud innervation and taste cell differentiation occur later in development. axolotl embryos are amenable to micr ...	2020	32044293
multiplex crispr/cas screen in regenerating haploid limbs of chimeric axolotls.	axolotls and other salamanders can regenerate entire limbs after amputation as adults, and much recent effort has sought to identify the molecular programs controlling this process. while targeted mutagenesis approaches like crispr/cas9 now permit gene-level investigation of these mechanisms, genetic screening in the axolotl requires an extensive commitment of time and space. previously, we quantified crispr/cas9-generated mutations in the limbs of mosaic mutant axolotls before and after regener ...	2020	31989926
the axolotl model for cancer research: a mini-review.	gastric cancer is the sixth most common cancer worldwide with increased associated morbidity and mortality. although a multimodality treatment approach is necessary, surgery is still considered as the standard of care. there is a longstanding intercontinental debate between eastern and western upper gi surgeons in regards to the proper type of lymphadenectomy that should accompany the resection of the primary tumor. while d2 gastrectomy was performed as the standard procedure in eastern countrie ...	2020	31983087
quantitative and qualitative behavioral measurements to assess pain in axolotls (ambystoma mexicanum).	effective pain relief in animals relies on the ability to discern pain and assess its severity. however, few objective measures exist to assess the presence and severity of pain in axolotls, and few resources are available regarding drugs and appropriate doses to provide pain relief in this species. this study evaluated behavioral tools for cageside pain assessment and validated a reproducible and reliable quantitative method to evaluate analgesic efficacy in axolotls. animals were divided into ...	2020	31964458
lag penalized weighted correlation for time series clustering.	the similarity or distance measure used for clustering can generate intuitive and interpretable clusters when it is tailored to the unique characteristics of the data. in time series datasets generated with high-throughput biological assays, measurements such as gene expression levels or protein phosphorylation intensities are collected sequentially over time, and the similarity score should capture this special temporal structure.	2020	31948388
operation spinal cord regeneration: patterning information residing in extracellular matrix glycosaminoglycans.	spinal cord injuries are devastating, with many complications beyond paralysis and loss of sensory function. although spinal cord regeneration can revolutionize treatment for spinal cord injuries, the goal has not yet been achieved. the regenerative mechanism of axolotls demonstrates that the regeneration is a repeat of developmental process that all animals have all the genes, but axolotls have both the genes and the patterning information to do it at the adult stage.	2020	31944630
midkine is a dual regulator of wound epidermis development and inflammation during the initiation of limb regeneration.	formation of a specialized wound epidermis is required to initiate salamander limb regeneration. yet little is known about the roles of the early wound epidermis during the initiation of regeneration and the mechanisms governing its development into the apical epithelial cap (aec), a signaling structure necessary for outgrowth and patterning of the regenerate. here, we elucidate the functions of the early wound epidermis, and further reveal midkine (mk) as a dual regulator of both aec developmen ...	2020	31934849
normal development in ambystoma mexicanum: a complementary staging table for the skull based on alizarin red s staining.	as the role of ambystoma mexicanum, or the mexican axolotl, expands in research applications beyond its traditional use in studies of limb regeneration, a staging table that is more anatomically extensive is required. here, we describe axolotl skull development as it relates to previously established developmental stages that were based on limb development.	2020	31930611
integrative analysis of axolotl gene expression data from regenerative and wound healing limb tissues.	axolotl (ambystoma mexicanum) is a urodele amphibian endowed with remarkable regenerative capacities manifested in scarless wound healing and restoration of amputated limbs, which makes it a powerful experimental model for regenerative biology and medicine. previous studies have utilized microarrays and rna-seq technologies for detecting differentially expressed (de) genes in different phases of the axolotl limb regeneration. however, sufficient consistency may be lacking due to statistical limi ...	2019	31889169
alginate hydrogel enriched with ambystoma mexicanum epidermal lipoxygenase-loaded pectin nanoparticles for enhanced wound healing.		2020	31886725
structure determination, functional characterization, and biosynthetic implications of nybomycin metabolites from a mining reclamation site-associated streptomyces.	we report the isolation and characterization of three new nybomycins (nybomycins b-d, 1-3) and six known compounds (nybomycin, 4; deoxynyboquinone, 5; α-rubromycin, 6; β-rubromycin, 7; γ-rubromycin, 8; and [2α(1e,3e),4β]-2-(1,3-pentadienyl)-4-piperidinol, 9) from the rock creek (mccreary county, ky) underground coal mine acid reclamation site isolate streptomyces sp. ad-3-6. nybomycin d (3) and deoxynyboquinone (5) displayed moderate (3) to potent (5) cancer cell line cytotoxicity and displayed ...	2019	31833370
extracting physiological information in experimental biology via eulerian video magnification.	videographic material of animals can contain inapparent signals, such as color changes or motion that hold information about physiological functions, such as heart and respiration rate, pulse wave velocity, and vocalization. eulerian video magnification allows the enhancement of such signals to enable their detection. the purpose of this study is to demonstrate how signals relevant to experimental physiology can be extracted from non-contact videographic material of animals.	2019	31831016
paradoxical changes underscore epigenetic reprogramming during adult zebrafish extraocular muscle regeneration.	genomic reprogramming and cellular dedifferentiation are critical to the success of de novo tissue regeneration in lower vertebrates such as zebrafish and axolotl. in tissue regeneration following injury or disease, differentiated cells must retain lineage while assuming a progenitor-like identity in order to repopulate the damaged tissue. understanding the epigenetic regulation of programmed cellular dedifferentiation provides unique insights into the biology of stem cells and cancer and may le ...	2019	31794598
advancements to the axolotl model for regeneration and aging.	loss of regenerative capacity is a normal part of aging. however, some organisms, such as the mexican axolotl, retain striking regenerative capacity throughout their lives. moreover, the development of age-related diseases is rare in this organism. in this review, we will explore how axolotls are used as a model system to study regenerative processes, the exciting new technological advancements now available for this model, and how we can apply the lessons we learn from studying regeneration in ...	2020	31779024
comparison of protein expression profile of limb regeneration between neotenic and metamorphic axolotl.	the axolotl (ambystoma mexicanum) salamander, a urodele amphibian, has an exceptional regenerative capacity to fully restore an amputated limb throughout the life-long lasting neoteny. by contrast, when axolotls are experimentally induced to metamorphosis, attenuation of the limb's regenerative competence is noticeable. here, we sought to discern the proteomic profiles of the early stages of blastema formation of neotenic and metamorphic axolotls after limb amputation by employing lc-ms/ms techn ...	2020	31767146
meningeal foam cells and ependymal cells in axolotl spinal cord regeneration.	a previously unreported population of foam cells (foamy macrophages) accumulates in the invasive fibrotic meninges during gap regeneration of transected adult axolotl spinal cord (salamander ambystoma mexicanum) and may act beneficially. multinucleated giant cells (mngcs) also occurred in the fibrotic meninges. actin-label localization and transmission electron microscopy showed characteristic foam cell and mngc podosome and ruffled border-containing sealing ring structures involved in substratu ...	2019	31736973
unique high sensitivity to heat of axolotl trpv1 revealed by the heterologous expression system.	the thermosensation mechanism plays critical roles in various animals living in different thermal environment. we focused on an axolotl, which is a tailed amphibian originally from lake xochimilco area in the vally of mexico, and examined its behavior response to heat stimulation. mild heat at 33 °c induced noxious locomotive activity to axolotls, but the noxious response of another tailed amphibian, iberian ribbed newt, was not observed at 33 °c. to explore the mechanism for the temperature sen ...	2020	31711646
contusion spinal cord injury via a microsurgical laminectomy in the regenerative axolotl.	the purpose of this study is to establish a standardized and reproducible regenerative blunt spinal cord injury model in the axolotl (ambystoma mexicanum). most clinical spinal cord injuries occur as high energy blunt traumas, inducing contusion injuries. however, most studies in the axolotl spinal cord have been conducted with sharp traumas. hence, this study aims to produce a more clinically relevant regenerative model. due to their impressive ability to regenerate almost any tissue, axolotls ...	2019	31680666
analysis of "old" proteins unmasks dynamic gradient of cartilage turnover in human limbs.	unlike highly regenerative animals, such as axolotls, humans are believed to be unable to counteract cumulative damage, such as repetitive joint use and injury that lead to the breakdown of cartilage and the development of osteoarthritis. turnover of insoluble collagen has been suggested to be very limited in human adult cartilage. the goal of this study was to explore protein turnover in articular cartilage from human lower limb joints. analyzing molecular clocks in the form of nonenzymatically ...	2019	31633025
oled loki as a catalyst for hydroxamate glycosylation.	herein we describe the ability of the permissive glycosyltransferase (gt) oled loki to convert a diverse set of >15 histone deacetylase (hdac) inhibitors (hdacis) into their corresponding hydroxamate glycosyl esters. representative glycosyl esters were subsequently evaluated in assays for cancer cell line cytotoxicity, chemical and enzymatic stability, and axolotl embryo tail regeneration. computational substrate docking models were predictive of enzyme-catalyzed turnover and suggest certain hda ...	2020	31621997
total synthesis of griseusins and elucidation of the griseusin mechanism of action.	a divergent modular strategy for the enantioselective total synthesis of 12 naturally-occurring griseusin type pyranonaphthoquinones and 8 structurally-similar analogues is described. key synthetic highlights include cu-catalyzed enantioselective boration-hydroxylation and hydroxyl-directed c-h olefination to afford the central pharmacophore followed by epoxidation-cyclization and maturation via diastereoselective reduction and regioselective acetylation. structural revision of griseusin d and a ...	2019	31583069
"lost and found": snorna annotation in the xenopus genome and implications for evolutionary studies.	small nucleolar rnas (snornas) function primarily as guide rnas for posttranscriptional modification of rrnas and spliceosomal snrnas, both of which are functionally important and evolutionarily conserved molecules. it is commonly believed that snornas and the modifications they mediate are highly conserved across species. however, most relevant data on snorna annotation and rna modification are limited to studies on human and yeast. here, we used rna-sequencing data from the giant oocyte nucleu ...	2020	31553476
fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development.	although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (aer). here, we investigated how sonic hedgehog (shh) and fibroblast growth factor (fgf) signaling regulate limb development in the axolotl. we found that shh-expressing cells contributed to the most posterior digit, and that inhibiti ...	2019	31538936
label-free imaging of tissue architecture during axolotl peripheral nerve regeneration in comparison to functional recovery.	human peripheral nerves hold the potential to regenerate after injuries; however, whether a successful axonal regrowth was achieved can be elucidated only months after injury by assessing function. the axolotl salamander is a regenerative model where nerves always regenerate quickly and fully after all types of injury. here, de- and regeneration of the axolotl sciatic nerve were investigated in a single and double injury model by label-free multiphoton imaging in comparison to functional recover ...	2019	31477751
a conserved regulatory program initiates lateral plate mesoderm emergence across chordates.	cardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (lpm). how the lpm initially emerges and how its downstream fates are molecularly interconnected remain unknown. here, we isolate a pan-lpm enhancer in the zebrafish-specific draculin (drl) gene that provides specific lpm reporter activity from early gastrulation. in toto live imaging and lineage tracing of drl-based reporters captures the dynamic lpm emerge ...	2019	31451684
lissamphibian limbs and the origins of tetrapod hox domains.	the expression and function of hox genes have played a key role in the debate on the evolution of limbs from fins. as an early branching tetrapod lineage, lissamphibians may provide information on the origin of the limb's hox domains and particularly how the plesiomorphic tetrapod pattern compares to the hox pattern present in fish fins. here, we comparatively investigated the expression of hox genes in the developing limbs of axolotl and xenopus laevis as well as in the fins of the direct devel ...	2019	31445923
stability and plasticity of positional memory during limb regeneration in ambystoma mexicanum.	urodele amphibians are capable of regenerating their organs after severe damage. during such regeneration, participating cells are given differentiation instructions by the surrounding cells. limb regeneration has been investigated as a representative phenomenon of organ regeneration. cells known as blastema cells are induced after limb amputation. in this process, dermal fibroblasts are dedifferentiated and become undifferentiated similar to limb bud cells. just like limb bud cells, the induced ...	2020	31386776
direct gene knock-out of axolotl spinal cord neural stem cells via electroporation of cas9 protein-grna complexes.	the axolotl has the unique ability to fully regenerate its spinal cord. this is largely due to the ependymal cells remaining as neural stem cells (nscs) throughout life, which proliferate to reform the ependymal tube and differentiate into lost neurons after spinal cord injury. deciphering how these nscs retain pluripotency post-development and proliferate upon spinal cord injury to reform the exact pre-injury structure can provide valuable insight into how mammalian spinal cords may regenerate ...	2019	31355781
model systems for regeneration: salamanders.	salamanders have been hailed as champions of regeneration, exhibiting a remarkable ability to regrow tissues, organs and even whole body parts, e.g. their limbs. as such, salamanders have provided key insights into the mechanisms by which cells, tissues and organs sense and regenerate missing or damaged parts. in this primer, we cover the evolutionary context in which salamanders emerged. we outline the varieties of mechanisms deployed during salamander regeneration, and discuss how these mechan ...	2019	31332037
cancer drug repositioning by comparison of gene expression in humans and axolotl (ambystoma mexicanum) during wound healing.	urodele amphibians such as the axolotl (ambystoma mexicanum) display a large capacity for tissue regeneration and remarkable resistance to cancer. as a model organism, axolotl thus offers a unique opportunity for cancer research and anticancer drug discovery, not to mention the discerning mechanisms that underpin controlled cellular growth and regeneration versus cancer. to the best of our knowledge, little is known on comparative gene expression changes during regeneration events such as wound ...	2019	31305215
hierarchical pattern formation during amphibian limb regeneration.	in 1901 t.h. morgan proposed in "regeneration" that pattern formation in amphibian limb regeneration is a stepwise process. since, biologist have continued to piece together the molecular components of this process to better understand the "patterning code" responsible for regenerate formation. within this context, several different models have been proposed; however, all are based on one of two underlying hypotheses. the first is the "morphogen hypothesis" that dictates that pattern emerges fro ...	2019	31295535
inhibiting fibroblast aggregation in skin wounds unlocks developmental pathway to regeneration.	salamanders are capable of full-thickness skin regeneration where removal of epidermis, dermis and hypodermis results in scar-free repair. what remains unclear is whether regeneration of these tissues recapitulates the cellular events of skin development or occurs through a process unique to regenerative healing. unfortunately, information on the post-embryonic development of salamander skin is severely lacking, having focused on compartments or cell types, but never on the skin as a complete or ...	2019	31279726
deep evolutionary origin of limb and fin regeneration.	salamanders and lungfishes are the only sarcopterygians (lobe-finned vertebrates) capable of paired appendage regeneration, regardless of the amputation level. among actinopterygians (ray-finned fishes), regeneration after amputation at the fin endoskeleton has only been demonstrated in polypterid fishes (cladistia). whether this ability evolved independently in sarcopterygians and actinopterygians or has a common origin remains unknown. here we combine fin regeneration assays and comparative rn ...	2019	31270239
treatment of chytridiomycosis in laboratory axolotls (ambystoma mexicanum) and rough-skinned newts (taricha granulosa).	chytridiomycosis is an infectious disease of amphibians caused by the fungal species batrachochytrium dendrobatidis and b. salamandrivorans and has been implicated in the population decline of amphibian species worldwide. this case report describes a successful treatment protocol for chytridiomycosis in laboratory-maintained colonies of axolotls (ambystoma mexicanum) and rough-skinned newts (taricha granulosa). over 12 mo, axolotls (n = 12) in a laboratory-reared colony developed multifocal eryt ...	2019	31142399
lineage tracing of sclerotome cells in amphibian reveals that multipotent somitic cells originate from lateral somitic frontier.	the two somite compartments, dorso-lateral dermomyotome and medio-ventral sclerotome are major vertebrate novelties, but little is known about their evolutionary origin. we determined that sclerotome cells in xenopus come from lateral somitic frontier (lsf) by lineage tracing, ablation experiments and histological analysis. we identified twist1 as marker of migrating sclerotome progenitors in two amphibians, xenopus and axolotl. from these results, three conclusions can be drawn. first, lsf is m ...	2019	31128088
longitudinal 16s rrna data derived from limb regenerative tissue samples of axolotl ambystoma mexicanum.	the mexican axolotl (ambystoma mexicanum) is a critically endangered species and a fruitful amphibian model for regenerative biology. despite growing body of research on the cellular and molecular biology of axolotl limb regeneration, microbiological aspects of this process remain poorly understood. here, we describe bacterial 16s rrna amplicon dataset derived from axolotl limb tissue samples in the course of limb regeneration. the raw data was obtained by sequencing v3-v4 region of 16s rrna gen ...	2019	31123261
endoscopic removal of a foreign body in a mexican axolotl (ambystoma mexicanum) with the use of ms222-induced immobilization.	this communication briefly describes the use of tricaine methanesulfonate (ms222) to induce chemical restraint/general anesthesia of a mexican axolotl (ambystoma mexicanum) for the endoscopic retrieval of a gastric foreign body. there is very little published scientific literature concerning the anesthesia of mexican axolotls. the anesthesia used in this case was an immersion bath of tricaine methanesulfonate where the concentration of tricaine methanesulfonate was gradually increased to 500 mg/ ...	2019	31120693
management of multiple protozoan ectoparasites in a research colony of axolotls (ambystoma mexicanum).	axolotls (ambystoma mexicanum) from a research colony presented with multifocal, white chalky to gray skin lesions, a diffuse whitish to blue hue to the integument, and friable gill filaments. skin scrapings and wet mounts revealed chilodonella, ichthyobodo, and a trichodinid species. the average overall burden (that is, all 3 species) per axolotl ranged from 0 to 25 parasites per 40 × field (p40f; mean ± 1 sd, 2.6 ± 5.5), with a prevalence of 12%, 60%, and 48%, respectively. concurrent with hus ...	2019	31060645
hdac regulates transcription at the outset of axolotl tail regeneration.	tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. we tested 172 compounds designed to target epigenetic mechanisms in an axolotl (ambystoma mexicanum) embryo tail regeneration assay. a relatively large number of compounds (n = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (hdaci). in particular, romidepsin, an fda-approved ...	2019	31043677
fgf- and bmp-signaling regulate gill regeneration in ambystoma mexicanum.	gill regeneration has not been well studied compared to regeneration of other appendages, such as limb and tail regeneration. here, we focused on axolotl gill regeneration and found that fgf- and bmp-signaling are involved in their gill regeneration mechanism. axolotls have three pairs of gill rami, and each gill ramus has multiple gill filaments. the gills consist of mesenchyme rich in extracellular matrix and epidermis. the gill nerves are supplied from the trigeminal ganglia located in the he ...	2019	31034835
rediscovering the axolotl as a model for thyroid hormone dependent development.	the mexican axolotl (ambystoma mexicanum) is an important model organism in biomedical research. much current attention is focused on the axolotl's amazing ability to regenerate tissues and whole organs after injury. however, not forgotten is the axolotl's equally amazing ability to thwart aspects of tissue maturation and retain juvenile morphology into the adult phase of life. unlike close tiger salamander relatives that undergo a thyroid hormone regulated metamorphosis, the axolotl does not ty ...	2019	31031711
fgf, bmp, and ra signaling are sufficient for the induction of complete limb regeneration from non-regenerating wounds on ambystoma mexicanum limbs.	some organisms, such as the mexican axolotl, have the capacity to regenerate complicated biological structures throughout their lives. which molecular pathways are sufficient to induce a complete endogenous regenerative response in injured tissue is an important question that remains unanswered. using a gain-of-function regeneration assay, known as the accessory limb model (alm), we and others have begun to identify the molecular underpinnings of the three essential requirements for limb regener ...	2019	31026439
effect of skeletal paracrine signals on the proliferation of interzone cells.	articular cartilage in mammals has limited intrinsic capacity to repair structural defects, a fact that contributes to the chronic and progressive nature of osteoarthritis. in contrast, mexican axolotl salamanders have demonstrated the remarkable ability to spontaneously and completely repair large joint cartilage lesions, a healing process that involves interzone cells in the intraarticular space. furthermore, interzone tissue transplanted into skeletal defects in the axolotl salamander demonst ...	2019	31023058
opposite t3 response of actg1-fos subnetwork differentiate tailfin fate in xenopus tadpole and post-hatching axolotl.	amphibian post-embryonic development and thyroid hormones (th) signaling are deeply and intimately connected. in anuran amphibians, th induce the spectacular and complex process known as metamorphosis. in paedomorphic salamanders, at similar development time, raising levels of th fail to induce proper metamorphosis, as many "larval" tissues (e.g., gills, tailfin) are maintained. why does the same evolutionary conserved signaling pathway leads to alternative phenotypes? we used a combination of d ...	2019	31001200
glycosaminoglycans compositional analysis of urodele axolotl (ambystoma mexicanum) and porcine retina.	retinal degenerative diseases, such as age-related macular degeneration (amd) and retinitis pigmentosa (rp), are major causes of blindness worldwide. humans cannot regenerate retina, however, axolotl (ambystoma mexicanum), a laboratory-bred salamander, can regenerate retinal tissue throughout adulthood. classic signaling pathways, including fibroblast growth factor (fgf), are involved in axolotl regeneration. glycosaminoglycan (gag) interaction with fgf is required for signal transduction in thi ...	2019	30963354
joints in the appendicular skeleton: developmental mechanisms and evolutionary influences.	the joints are a diverse group of skeletal structures, and their genesis, morphogenesis, and acquisition of specialized tissues have intrigued biologists for decades. here we review past and recent studies on important aspects of joint development, including the roles of the interzone and morphogenesis of articular cartilage. studies have documented the requirement of interzone cells in limb joint initiation and formation of most, if not all, joint tissues. we highlight these studies and also re ...	2019	30902250
a clinically relevant blunt spinal cord injury model in the regeneration competent axolotl (ambystoma mexicanum) tail.	a randomized controlled and blinded animal trial was conducted in the axolotl (ambystoma mexicanum), which has the ability to regenerate from transectional spinal cord injury (sci). the objective of the present study was to investigate the axolotl's ability to regenerate from a blunt spinal cord trauma in a clinical setting. axolotls were block-randomized to the intervention (n=6) or sham group (n=6). a laminectomy of two vertebrae at the level caudal to the hind limbs was performed. to induce a ...	2019	30867717
ap-1cfos/junb/mir-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration.	salamanders have the remarkable ability to functionally regenerate after spinal cord transection. in response to injury, gfap+ glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. here we show axolotl glial cells up-regulate ap-1cfos/junb after injury, which promotes a pro-regenerative glia ...	2019	30854483
nerve-mediated expression of histone deacetylases regulates limb regeneration in axolotls.	axolotls have amazing abilities to regenerate their lost limbs. nerve and wound epidermis have great impacts on this regeneration. histone deacetylases (hdacs) have been shown to play roles in the regeneration of amphibian tails and limbs. in this study, a bi-phasic up-regulation of hdac1 was noted before early differentiation stage of axolotl limb regeneration. limb regeneration was delayed in larvae incubated with an hdac inhibitor ms-275. local injection of ms-275 or tsa, another hdac inhibit ...	2019	30826398
investigating nrg1 signaling in the regenerating axolotl spinal cord using multiplexed fish.	amputation of a salamander tail leads to functional spinal cord regeneration through activation of endogenous stem cells. identifying the signaling pathways that control cell proliferation in these neural stem cells will help elucidate the mechanisms underlying the salamander's regenerative ability. here, we show that neuregulin 1 (nrg1)/erbb2 signaling is an important pathway in the regulation of neural stem cell proliferation in the spinal cord of the axolotl salamander (ambystoma mexicanum). ...	2019	30793850
epithelial to mesenchymal transition is mediated by both tgf-β canonical and non-canonical signaling during axolotl limb regeneration.	axolotls have the amazing ability to regenerate. when compared to humans, axolotls display a very fast wound closure, no scarring and are capable to replace lost appendages perfectly. understanding the signaling mechanism leading to this perfect healing is a key step to help develop regenerative treatments for humans. in this paper, we studied cellular pathways leading to axolotl limb regeneration. we focus on the wound closure phase where keratinocytes migrate to close the lesion site and how e ...	2019	30718780
functional properties of axolotl transient receptor potential ankyrin 1 revealed by the heterologous expression system.	transient receptor potential ankyrin 1 (trpa1) from tetrapod vertebrates except rodents are activated by high temperature with a relatively clear threshold. our recent investigation suggested that a gradual heat activation without clear threshold might be a common feature for trpa1 of fish. to approach which animal first acquires trpa1 as a threshold detector instead of a gradual heat sensor, here, we focused on trpa1 from axolotls (ambystoma mexicanum). we isolated a full-length cdna of axolotl ...	2019	30702505
publisher correction: application and optimization of crispr-cas9-mediated genome engineering in axolotl (ambystoma mexicanum).	in the version of this protocol originally published, the recipe for cas9 buffer was incorrectly identified as a recipe for sodium acetate solution, and vice versa. these errors have been corrected in the pdf and html versions of the paper.	2019	30696984
a chromosome-scale assembly of the axolotl genome.	the axolotl (ambystoma mexicanum) provides critical models for studying regeneration, evolution, and development. however, its large genome (∼32 gb) presents a formidable barrier to genetic analyses. recent efforts have yielded genome assemblies consisting of thousands of unordered scaffolds that resolve gene structures, but do not yet permit large-scale analyses of genome structure and function. we adapted an established mapping approach to leverage dense snp typing information and for the firs ...	2019	30679309
broad applicability of a streamlined ethyl cinnamate-based clearing procedure.	turbidity and opaqueness are inherent properties of tissues that limit the capacity to acquire microscopic images through large tissues. creating a uniform refractive index, known as tissue clearing, overcomes most of these issues. these methods have enabled researchers to image large and complex 3d structures with unprecedented depth and resolution. however, tissue clearing has been adopted to a limited extent due to a combination of cost, time, complexity of existing methods and potential nega ...	2019	30665888
blastemal progenitors modulate immune signaling during early limb regeneration.	blastema formation, a hallmark of limb regeneration, requires proliferation and migration of progenitors to the amputation plane. although blastema formation has been well described, the transcriptional programs that drive blastemal progenitors remain unknown. we transcriptionally profiled dividing and non-dividing cells in regenerating stump tissues, as well as the wound epidermis, during early axolotl limb regeneration. our analysis revealed unique transcriptional signatures of early dividing ...	2019	30602532