Presence of immune cells in the regenerating caudal spinal cord of frog tadpoles indicates active immune-surveillance before metamorphosis (original) (raw)
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Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis
Developmental Immunology, 1992
Metamorphosis in amphibians presents a unique problem for the developing immune system. Because tadpoles are free-living, they need an immune system to protect against potential pathogens. However, at metamorphosis, they acquire a variety of new adultspecific molecules to which the tadpole immune system must become tolerant. We hypothesized thatXenopus laevistadpoles may avoid potentially destructive antiself responses by largely discarding the larval immune system at metamorphosis and acquiring a new one. By implanting triploid (3N) thymuses into diploid (2N) hosts, we examined the influx and expansion of host T-cell precursors in the donor thymus of normally metamorphosing and metamorphosis-inhibited frogs. We observed that donor thymocytes are replaced by host-derived cells during metamorphosis, but inhibition of metamorphosis does not prevent this exchange of cells. The implanted thymuses export T cells to the spleen. This donor-derived pool of cells declines after metamorphosis...
Development, 2009
Regenerative ability varies depending on animal species and developmental stage, but the factors that determine this variability remain unclear. Although Xenopus laevis tadpole tails possess high regenerative ability, this is transiently lost during the 'refractory period'. Here, we show that tail amputation evokes different immune responses in wound tail stumps between the 'refractory' and 'regeneration' periods: there was delayed or prolonged expression of some immune-related genes in the refractory period, whereas there was no obvious or transient expression of other immune-related genes in the regeneration periods. In addition, immune suppression induced by either immunosuppressant treatment or immune cell depletion by knockdown of PU.1 significantly restored regenerative ability during the refractory period. These findings indicate that immune responses have a crucial role in determining regenerative ability in Xenopus tadpole tails.
The antibody response during amphibian ontogeny
Immunogenetics, 1976
The maturation of the anti DNP-response in adult and larval amphibians has been compared in two species of anurans, Rana catesbeiana and Xenopus laevis. IgM responses were very similar in larvae and adults of both species. Specific IgG antibody synthesis, studied in Rana catesbeiana only, was not obvious in larval primary response but was easily detectable in adults. Although metamorphosis results in profound changes in the lymphoid system associated with the apparent acquisition of self tolerance to new antigens, immunological memory of antigens injected during larval life of Rana and Yenopus persists after the metamorphosis period.
Limb Regeneration in Amphibians: Immunological Considerations
TSW Development & Embryology, 2006
We review key aspects of what is known about limb regeneration in urodele and anuran amphibians, with a focus on the early events of the process that lead to formation of the regeneration blastema. This includes the role of the nerves and wound epithelium, but also covers the inflammatory effects of the amputation trauma and their importance for regenerative growth. We propose that immunotolerance is important for limb regeneration and changes in its regulation may underlie the loss of regenerative capacity during anuran metamorphosis.
Journal of Experimental Biology, 2014
Recent hypotheses suggest that immunosuppression, resulting from altered environmental conditions, may contribute to the increased incidence of amphibian disease around the world. Antimicrobial peptides (AMPs) in amphibian skin are an important innate immune defense against fungal, viral and bacterial pathogens. Their release is tightly coupled with release of the stress hormone noradrenaline (norepinephrine). During metamorphosis, AMPs may constitute the primary immune response in the skin of some species because acquired immune functions are temporarily suppressed in order to prevent autoimmunity against new adult antigens. Suppression of AMPs during this transitional stage may impact disease rates. We exposed leopard frog tadpoles (Lithobates pipiens) to a factorial combination of competitor and caged-predator environments and measured their development, growth and production of hydrophobic skin peptides after metamorphosis. In the absence of predator cues, or if the exposure to predator cues was late in ontogeny, competition caused more than a 250% increase in mass-standardized hydrophobic skin peptides. Predator cues caused a decrease in mass-standardized hydrophobic skin peptides when the exposure was late in ontogeny under low competition, but otherwise had no effect. Liquid chromatography tandem mass spectrometry of the skin peptides showed that they include six AMPs in the brevinin and temporin families and at least three of these peptides are previously uncharacterized. Both of these peptide families have previously been shown to inhibit harmful microbes including Batrachochytrium dendrobatidis, the fungal pathogen associated with global amphibian declines. Our study shows that amphibians may be able to adjust their skin peptide defenses in response to stressors that are experienced early in ontogeny and that these effects extend through an important life-history transition.
In Vitro Cellular & Developmental Biology - Animal, 2011
Larval-to-adult myogenic conversion occurs in the dorsal muscle but not in the tail muscle during Xenopus laevis metamorphosis. To know the mechanism for tail-specific suppression of adult myogenesis, response character was compared between adult myogenic cells (Ad-cells) and larval tail myogenic cells (La-cells) to a Sonic hedgehog (Shh) inhibitor, notochord (Nc) cells, and spinal cord (SC) cells in vitro. Cyclopamine, an Shh inhibitor, suppressed the differentiation of cultured Ad (but not La) cells, suggesting the significance of Shh signaling in promoting adult myogenesis. To test the possibility that Shh-producing axial elements (notochord and spinal cord) regulate adult myogenesis, Ad-cells or La-cells were co-cultured with Nc or SC cells. The results showed that differentiation of Ad-cells were strongly inhibited by Nc cells but promoted by SC cells. If Ad-cells were "separately" co-cultured with Nc cells without direct cell-cell interactions, adult differentiation was not inhibited but rather promoted, suggesting that Nc cells have two roles, one is a short-range suppression and another is a long-range promotion for adult myogenesis. Immunohistochemical analysis showed both notochord and spinal cord express the N-terminal Shh fragment throughout metamorphosis. The "spinal cord-promotion" and long-range effect by Nc cells on adult myogenesis is thus involved in Shh signaling, while the signaling concerning the short-range "Nc suppression" will be determined by future studies. Interestingly, these effects, "Nc suppression" and "SC promotion" were not observed for La-cells. Situation where the spinal cord/notochord cross-sectional ratio is quite larger in tadpole trunk than in the tail seems to contribute to trunk-specific promotion and tail-specific suppression of adult myogenesis during Xenopus metamorphosis.
Development, Growth and Differentiation, 2002
It has been shown that larval skin (LS) grafts are rejected by an inbred strain of adult Xenopus , which suggests a mechanism of metamorphosis by which larval cells are recognized and attacked by the newly differentiating immune system, including T lymphocytes. In an attempt to define the larval antigenic molecules that are targeted by the adult immune system, anti-LS antibodies (IgY) were produced by immunizing adult frogs with syngeneic LS grafts. The antigen molecules that reacted specifically with this anti-LS antiserum were localized only in the larval epidermal cells. Of 53 and 59-60 kDa acidic proteins that were reactive with anti-LS antibodies, a protein of 59 kDa and with an isoelectric point of 4.5 was selected for determination of a 19 amino acid sequence (larval peptide). The rat antiserum raised against this peptide was specifically reactive with the 59 kDa molecules of LS lysates. Immunofluorescence studies using these antisera revealed that the larvalspecific molecules were localized in both the tail and trunk epidermis of premetamorphic larvae, but were reduced in the trunk regions during metamorphosis, and at the climax stage of metamorphosis were detected only in the regressing tail epidermis. Culture of splenocytes from LS-immunized adult frogs in the presence of larval peptide induced augmented proliferative responses. Cultures of larval tail pieces in T cell-enriched splenocytes from normal frogs or in natural killer (NK)-cell-enriched splenocytes from early thymectomized frogs both resulted in significant destruction of tail pieces. Tissue destruction in the latter was enhanced when anti-LS antiserum was added to the culture. These results indicate that degeneration of tail tissues during metamorphosis is induced by a mechanism such that the larval-specific antigen molecules expressed in the tail epidermis are recognized as foreign by the newly developing adult immune system, and destroyed by cytotoxic T lymphocytes and/or NK cells.
Expression Changes of MHC and Other Immune Genes in Frog Skin during Ontogeny
Animals
Anuran amphibians undergo major physiological and immunological changes following metamorphosis. Genes of the major histocompatibility complex (MHC) code for receptors important for vertebrate adaptive immunity. We used qPCR to measure skin MHC expression in six different ontological stages of Rana ornativentris (n = 10 per stage); normalized MHC class I and II expression at the mRNA level was significantly higher in stage 28 (mid-larval) compared to stages 24/25 (early-larval) tadpoles. Subsequent transcriptomic analyses of three tadpole (early-, mid-, and late-larval) stages of R. ornativentris and model species Xenopus tropicalis focused on mRNA expression of immune-related genes in the skin. Normalized expression of most MHC class I and II transcripts in both species were significantly higher in mid- and late-larval stages compared to early-larval stage. In addition, gene ontology (GO) analyses of differentially expressed transcripts revealed several immune-related GO terms that...