Differential gene expression analysis between pre-metamorphic WT control X. laevis tadpoles and tadpoles with thioridazine-induced brain abnormalities.
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ABSTRACT:
ORGANISM(S): Xenopus laevis
PROVIDER: GSE129234 | GEO | 2019/08/15
REPOSITORIES: GEO
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Project description:We found 101 differentially expressed genes between control and thioridazine samples at NF stage 45 and 135 at NF stage 47.
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Project description:Differential gene expression analysis between pre-metamorphic WT control X. laevis tadpoles and tadpoles with thioridazine-induced brain abnormalities.
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Project description:AbstractStudies on the impacts of variation of biotic interactions at key life cycle stages are crucial to understand the interface between ecological and developmental processes. Predators exert a major impact on prey fitness. Although direct consumption entails the greatest effect, predators can affect prey by means of other mechanisms. For instance, injuries inflicted by failed predation attempts can jeopardize prey fitness, even beyond the short-term. In anuran tadpoles, failed predation typically results in partial tail loss, which is known to reduce swimming speed. However, the potential consequences of tadpole partial tail loss after metamorphosis remain understudied. Because tail materials could be important in conforming metamorph body, we assess the effects of tadpole partial tail loss on metamorph body size in Iberian spadefoot toads Pelobates cultripes. We clipped 55% tail length of pre-tail-resorption stage anesthetized tadpoles, and compared their body size as metamorphs with anesthetized and non-anesthetized non-tail-clipped controls. Also, we tested whether tail length correlated with metamorph body size of individuals of the control groups. Tail-clipped tadpoles produced smaller metamorphs than both controls (the bdy size of metamorphs from both controls was similar), which could incur costs in mid-term survival or time to first reproduction. This effect could be particularly important in areas with introduced predators, if autochthonous tadpoles lack defenses against them. Results suggest that materials resorbed from tadpole tail tissues might be reallocated into metamorph body, according to the negative effect of shorter tails in a correlational analysis, and clipped tails in an experimental test, on metamorph body size.
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Project description:We conducted differential gene expression analyses of the developing X. laevis tadpole midbrain between stages 44 and 61, and across brain regions at stage 46. We found that genes pertaining to positive regulation of neural progenitor cell proliferation as well as known progenitor cell markers were upregulated in the midbrain prior to metamorphic climax; concurrently, expression of cell cycle timing regulators decreased across this period. We also found that at the start of metamorphosis, neural progenitor populations appeared to be similar across the fore-, mid-, and hindbrain regions. Genes pertaining to negative regulation of differentiation were upregulated in the spinal cord compared to the rest of the brain. Finally, we found that regulation of biological processes like cell fate commitment and synaptic signaling follow similar trajectories in the brain across early tadpole metamorphosis and mid- to late-embryonic mouse development.
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Project description:The role of growth hormone (GH) in amphibian metamorphosis is ambiguous based on experiments in which mammalian GH was administered to tadpoles and frogs. We have reexamined the effects of GH by producing transgenic Xenopus laevis that overexpress the cDNA encoding X. laevis GH. These transgenic tadpoles take the same length of time to reach metamorphosis as control tadpoles, but the transgenic tadpoles are twice as large. After metamorphosis, the transgenic frogs grow at a greatly accelerated rate and develop skeletal abnormalities reminiscent of acromegaly. The transgenic frogs are larger than mature frogs in a few months and die in about 1 year. At as early as 10 months of age, the males have mature sperm. We conclude that the growth-promoting effects of GH in this amphibian closely resemble those described for mammals. Although excess GH increases the size of the tadpole, it does not alter the developmental programs involved in metamorphosis.
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Project description:Amphibian metamorphosis is a transitional period that involves significant changes in the cell type populations and biological processes occurring in the brain. Analysis of gene expression dynamics during this process may provide insight into the molecular events underlying these changes. We conducted differential gene expression analyses of the developing X. laevis tadpole brain during this period in two ways: first, over stages of development in the midbrain, and second, across regions of the brain at a single developmental stage. We found that genes pertaining to positive regulation of neural progenitor cell proliferation as well as known progenitor cell markers were upregulated in the midbrain prior to metamorphic climax; concurrently, expression of cell cycle timing regulators decreased across this period, supporting the notion that cell cycle lengthening contributes to a decrease in proliferation by the end of metamorphosis. We also found that at the start of metamorphosis, neural progenitor populations appeared to be similar across the fore-, mid-, and hindbrain regions. Genes pertaining to negative regulation of differentiation were upregulated in the spinal cord compared to the rest of the brain, however, suggesting that a different program may regulate neurogenesis there. Finally, we found that regulation of biological processes like cell fate commitment and synaptic signaling follow similar trajectories in the brain across early tadpole metamorphosis and mid- to late-embryonic mouse development. By comparing expression across both temporal and spatial conditions, we have been able to illuminate cell type and biological pathway dynamics in the brain during metamorphosis.
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Project description:Appropriate thyroid hormone (TH) signaling through thyroid hormone receptors (TRs) is essential for vertebrate development. Amphibian metamorphosis is initiated and sustained through the action of TH on TRs, which are conserved across vertebrates. TRs heterodimerize with retinoid X receptors (RXRs) on thyroid hormone response elements (TREs) in the genome; however, in most cell line and adult animal studies, RXR ligands do not affect expression of TR target genes. We used a quantitative, precocious metamorphosis assay to interrogate the effects of the RXR agonist bexarotene (Bex) and the RXR antagonist UVI 3003 (UVI) on T3-induced resorption phenotypes in Xenopus laevis tadpoles 1 week postfertilization. Bex potentiated gill and tail resorption, and UVI abrogated T3 action. These results held in transgenic tadpoles bearing a TRE-driven luciferase reporter. Therefore, we used poly-A-primed RNA sequencing transcriptomic analysis to determine their effects on T3-induced gene expression. We also assayed the environmental pollutant tributyltin (TBT), which is an RXR agonist. We found that the proteases that carry out resorption were potentiated by Bex and TBT but were not significantly inhibited by UVI. However, several transcription factors from multiple families (sox4, fosl2, mxd1, mafb, nfib) were all inhibited by UVI and potentiated by Bex and TBT. All required T3 for induction. Time course analysis of gene expression showed that although the agonists could potentiate within 12 hours, the antagonist response lagged. These data indicate that the agonists and antagonist are not necessarily functioning through the same mechanism and suggest that RXR liganding may modulate TH competence in metamorphic signaling.
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