scholarly journals Fluctuation of cellular differentiation in limb regeneration is regulated by Pde4b in urodele amphibians

2021 ◽  
Author(s):  
Akira Satoh ◽  
Rena Kashimoto ◽  
Ayaka Ohashi ◽  
Saya Furukawa ◽  
Sakiya Yamamoto ◽  
...  
Keyword(s):  
Cellular Differentiation ◽  
Limb Regeneration ◽  
Cell Lineage ◽  
Dermal Fibroblasts ◽  
Ambystoma Mexicanum ◽  
Valuable Insight ◽  
Multipotent Cells ◽  
Regeneration Capability ◽  
Pleurodeles Waltl ◽  
Knockout Animals

Urodele amphibians, Pleurodeles waltl and Ambystoma mexicanum, have organ level regeneration capability, such as limb regeneration. Multipotent cells are induced by an endogenous mechanism in amphibian limb regeneration. It is well known that dermal fibroblasts receive regenerative signals and turn into multipotent cells, called blastema cells. However, the induction mechanism of the blastema cells from matured dermal cells was unknown. We previously found that BMP2, FGF2, and FGF8 (B2FF) could play sufficient roles in blastema induction in urodele amphibians. Here, we show that B2 FF treatment can induce dermis derived cells that can participate in multiple cell lineage in limb regeneration. We first established a newt dermis derived cell line and confirmed that B2FF treatment on the newt cells provided plasticity in cellular differentiation in limb regeneration. Interspecies comparative analysis clarified that Pde4b upregulation by B2FF specifically took place in the newt cells. Blocking P DE4B signaling by Rolipram suppressed dermis to cartilage transformation and the mosaic knockout animals showed consistent results . Our results are a valuable insight into how dermal fibroblasts acquire multipotency during the early phase of limb regeneration via an endogenous program in amphibian limb regeneration.

Citral, an inhibitor of retinoic acid synthesis, modifies pattern formation during limb regeneration in the axolotl Ambystoma mexicanum

1999 ◽  
Vol 77 (11) ◽  
pp. 1835-1837 ◽  
Author(s):  
Steven R Scadding
Keyword(s):  
Retinoic Acid ◽  
Pattern Formation ◽  
Limb Regeneration ◽  
Acid Synthesis ◽  
Ambystoma Mexicanum

While the effects of exogenous retinoids on amphibian limb regeneration have been studied extensively, the role of endogenous retinoids is not clear. Hence, I wished to investigate the role of endogenous retinoic acid during axolotl limb regeneration. Citral is a known inhibitor of retinoic acid synthesis. Thus, I treated regenerating limbs of the larval axolotl Ambystoma mexicanum with citral. The result of this inhibition of retinoic acid synthesis was that limb regeneration became extremely irregular and hypomorphic, with serious pattern defects, or was inhibited altogether. I conclude that endogenous retinoic acid plays an important role in pattern formation during limb regeneration.

Symmetrical vascularization patterns in normal and retinoic acid treated limb regenerates of the axolotl, Ambystoma mexicanum

1998 ◽  
Vol 76 (9) ◽  
pp. 1795-1796 ◽  
Author(s):  
Steven R Scadding ◽  
Andrew Burns
Keyword(s):  
Retinoic Acid ◽  
Pattern Formation ◽  
Vascular System ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Limb Pattern ◽  
Regeneration Blastema

The purpose of this investigation was to determine whether there were any asymmetries in the vascularization of the limb-regeneration blastema in the axolotl, Ambystoma mexicanum, that might be related to pattern formation, and to determine if retinoic acid could modify the vascular patterns of the blastema. We used acrylic casts of the vascular system of the limbs to assess the pattern of vascularization. We observed a very regular symmetrical arrangement of capillaries in the limb-regeneration blastema that did not appear to be modified by doses of retinoic acid sufficient to modify the limb pattern.

The influence of aminopterin on limb regeneration in Ambystoma mexicanum

Development ◽  
1966 ◽  
Vol 16 (1) ◽  
pp. 143-158
Author(s):  
D. O. E. Gebhardt ◽  
J. Faber
Keyword(s):  
Toluidine Blue ◽  
Growth Retardation ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Ontogenetic Development ◽  
Antimitotic Agent ◽  
Chemical Substances ◽  
Histamine Formation ◽  
Number Of Authors

During the last twenty-five years a number of authors have studied the influence of chemical substances on limb regeneration in amphibians. Examples of compounds which have been tested so far are: (1) the antimitotic agent, colchicine (Thornton, 1943); (2) the salt, beryllium nitrate (Thornton, 1949, 1950, 1951); (3) the carcinogens, dibenzanthracene and methylcholanthrene (Karczmar & Berg, 1952; Ruben & Balls, 1964); (4) the lathyrus factor, β- aminopropionitrile (Chang, Witschi & Ponseti, 1955); (5) the hormone, thyroxine (Hay, 1956); (6) atropine and other neuropharmacological drugs (Singer, Davis & Scheuing, 1960); (7) the metachromatic dye, toluidine blue (Csaba, Bierbauer & Törö, 1961); and (8) semicarbazide, an inhibitor of histamine formation (Deck & Shapiro, 1963). Most of these substances caused growth retardation as well as malformations of the limb regenerates. A number of other investigators have studied the effects of chemicals on the ontogenetic development of the amphibian limb.

Role of bilateral zones of ingressing superficial cells during gastrulation of Ambystoma mexicanum

Development ◽  
1986 ◽  
Vol 97 (1) ◽  
pp. 47-62
Author(s):  
Cathy Lundmark
Keyword(s):  
Cell Lineage ◽  
Dorsal Surface ◽  
Ambystoma Mexicanum ◽  
Epithelial Layer ◽  
Dorsal Midline ◽  
Morphogenetic Movements ◽  
Vital Dye ◽  
Dye Staining ◽  
Somitic Mesoderm

Vital dye staining and cell lineage tracers were used to mark superficial cells of early Ambystoma mexicanum gastrulae. Superficial marks placed between the equator and the blastopore, on the dorsal midline, stained notochord, whereas marks or injections made at similar animal—vegetal levels but 90° to either side of the dorsal midline were later found in somitic mesoderm. Notochord marks remained on the dorsal surface of the archenteron throughout gastrulation, though they became elongate and narrow by the morphogenetic movements of extension and convergence. Marked somitic mesoderm disappeared from the superficial epithelial layer soon after passing over the blastoporal lip and could not be found on the archenteron surface. A possible mechanism for this de-epithelialization is proposed on the basis of correlated SEM. The significance of a method of gastrulation so distinctly different from that of certain other amphibians is discussed in terms of amphibian phylogeny.

scholarly journals Conservation analysis of core cell cycle regulators and their transcriptional behavior during limb regeneration in Ambystoma mexicanum

2020 ◽  
Vol 164 ◽  
pp. 103651
Author(s):  
Annie Espinal-Centeno ◽  
Melissa Dipp-Álvarez ◽  
Carlos Saldaña ◽  
Laszlo Bako ◽  
Alfredo Cruz-Ramírez
Keyword(s):  
Cell Cycle ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Cell Cycle Regulators ◽  
Conservation Analysis

Skeletal patterns in the autopodium of native and regenerated limbs of the larval axolotl, Ambystoma mexicanum

1991 ◽  
Vol 69 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Steven R. Scadding
Keyword(s):  
Vitamin A ◽  
Significant Variation ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Skeletal Patterning ◽  
Skeletal Pattern ◽  
Limb Pattern ◽  
Salamander Species

The purpose of this investigation was to study the autopodial skeletal patterns that are observed in native (never regenerated) and regenerated limbs of the larval axolotl, Ambystoma mexicanum. The axolotl is used widely in limb regeneration studies, and in the regenerating axolotl limb mesopodial patterns can be modified by such factors as vitamin A administration. It is also known that other salamander species show significant variation in autopodial skeletal patterning. Hence, it seemed important to determine the type and frequency of autopodial variants in both native limbs and those that have regenerated after amputation at either the stylopodial and zeugopodial levels. The results showed that native limbs exhibited a complete skeletal pattern in the majority of cases, but that variants involving loss of a phalange or reduction in the number of carpals or tarsals occurred frequently. Regenerated limb patterns were more variable than those seen in native limbs, and limbs regenerating from zeugopodial level amputations were more variable than those regenerating from stylopodial level amputation. The significance of these observations for the development and regeneration of limb pattern is discussed.

scholarly journals Integrative Analysis of Axolotl Gene Expression Data From Regenerative and Wound Healing Limb Tissues

2019 ◽  
Author(s):  
Mustafa Sibai ◽  
Cüneyd Parlayan ◽  
Pelin Tuğlu ◽  
Gürkan Öztürk ◽  
Turan Demircan
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Differential Expression Analysis ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Integrative Analysis ◽  
Control Group ◽  
Rna Seq ◽  
Amputation Injury ◽  
Study Designs

ABSTRACTAxolotl (Ambystoma mexicanum) is a urodele amphibian endowed with remarkable regenerative capacities manifested in scarless wound healing and full restoration of amputated limbs. Several regenerative cues of the axolotl limb were successfully unraveled due to the advent of high-throughput technologies and their employment in tackling research questions on several OMICS levels. The field of regenerative biology and medicine has therefore utilized the axolotl as a major and powerful experimental model. Studies which have previously unraveled differentially expressed (DE) genes en masse in different phases of the axolotl limb regeneration have primarily used microarrays and RNA-Seq technologies. However, as different labs are conducting such experiments, sufficient consistency may be lacking due to statistical limitations arising from limited number of sample replicates as well as possible differences in study designs. This study, therefore, aims to bridge such gaps by performing an integrative analysis of publicly available microarray and RNA-Seq data from axolotl limb samples having comparable study designs. Three biological groups were conceived for the analysis; homeostatic tissues (control group), from amputation/injury timepoint up to around 50 hours post amputation (wound healing group), and from 50 hours to 28 days post amputation/injury (regenerative group). Integrative analysis was separately carried out on the selected microarray and RNA-Seq data from axolotl limb samples using the “merging” method. Differential expression analysis was separately implemented on the processed data from both technologies using the R/Bioconductor “limma” package. A total of 1254 genes (adjusted P < 0.01) were found DE in regenerative samples compared to the control, out of which 351 showed magnitudes of Log Fold Changes (LogFC) > 1 and were identified as the top DE genes from data of both technologies. Downstream analyses illustrated consistent correlations of the logFCs of DE genes distributed among the biological comparisons, within and between both technologies. Gene ontology annotations demonstrated concordance with the literature on the biological process involved in the axolotl limb regeneration. qPCR analysis validated the observed gene expression level differences between regenerative and control samples for a set of five genes. Future studies may benefit from the utilized concept and approach for enhanced statistical power and robust discovery of biomarkers of regeneration.

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