<scp>T</scp>ranscriptional dynamics of tail regeneration in <i>Xenopus tropicalis</i>

Chang, Jessica; Baker, Julie C.; Wills, Andrea E.

doi:10.1002/dvg.23015

Cited by 27 publications

(32 citation statements)

References 28 publications

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“…Studies of the refractory period have also implicated the importance of inflammatory processes during tail regeneration. In regeneration-competent X. tropicalis tadpoles, inflammatory cells are recruited to the wound site over the first 6 h post-amputation (hpa) (Love et al, 2011a), in line with genome-wide studies in Xenopus, which demonstrated an enrichment of inflammation-associated genes during the early phase of regeneration (Aztekin et al, 2019;Chang et al, 2017;Love et al, 2011a). In the refractory period, however, inappropriate activation of the immune system may impair tail regeneration, as immunosuppression improves regeneration in these animals (Fukazawa et al, 2009).…”

Section: Insights Gained From Studying Regeneration In Xenopus Appendmentioning

confidence: 65%

Model systems for regeneration: Xenopus

et al. 2020

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Understanding how to promote organ and appendage regeneration is a key goal of regenerative medicine. The frog, Xenopus, can achieve both scar-free healing and tissue regeneration during its larval stages, although it predominantly loses these abilities during metamorphosis and adulthood. This transient regenerative capacity, alongside their close evolutionary relationship with humans, makes Xenopus an attractive model to uncover the mechanisms underlying functional regeneration. Here, we present an overview of Xenopus as a key model organism for regeneration research and highlight how studies of Xenopus have led to new insights into the mechanisms governing regeneration.

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Section: Insights Gained From Studying Regeneration In Xenopus Appendmentioning

confidence: 65%

Model systems for regeneration: Xenopus

et al. 2020

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“…5a), we found that 115 genes (and 37 unique) were responsive to brain removal per se. To characterize the transcriptional response specifically due to brain removal, and not to the removal of any organ in general, we compared the dataset of DEGs after brain removal from our study with the DEGs obtained after tail removal that were identified in two prior studies, in Xenopus 53 and lizard. 54 The tail is large appendage including a massive CNS component (spinal cord) and triggers a robust regenerative response, allowing us to identify and exclude Fig.…”

Section: Brain Is Required For Migratory Response Of Macrophagesmentioning

confidence: 99%

An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity

et al. 2020

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Infections have numerous effects on the brain. However, possible roles of the brain in protecting against infection, and the developmental origin and role of brain signaling in immune response, are largely unknown. We exploited a unique Xenopus embryonic model to reveal control of innate immune response to pathogenic E. coli by the developing brain. Using survival assays, morphological analysis of innate immune cells and apoptosis, and RNA-seq, we analyzed combinations of infection, brain removal, and tail-regenerative response. Without a brain, survival of embryos injected with bacteria decreased significantly. The protective effect of the developing brain was mediated by decrease of the infection-induced damage and of apoptosis, and increase of macrophage migration, as well as suppression of the transcriptional consequences of the infection, all of which decrease susceptibility to pathogen. Functional and pharmacological assays implicated dopamine signaling in the bacteria-brain-immune crosstalk. Our data establish a model that reveals the very early brain to be a central player in innate immunity, identify the developmental origins of brain-immune interactions, and suggest several targets for immune therapies.

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“…All the statistical tests were done using Prism 8. and day 3 (SC_d0d3). The whole tail dataset was obtained from [9]. (E) Tadpoles at NF50 were amputated, fixed at the indicated time and then processed for WISH using a probe specific for foxm1.…”

Section: Statisticsmentioning

confidence: 99%

“…Using Ingenuity Pathway Analysis (IPA), we identified potential upstream regulators that could explain changes in expression of downstream target genes, with Foxm1 showing the highest significance at 3dpa ( Figure 1C). Using published RNAseq of tail regeneration in X.tropicalis [9], we compared changes in expression of known Foxm1 target genes between 0 and 3dpa in whole tail (WT_d0d3), 0 and 1dpa (SC_d0d1) and 0 and 3dpa (SC_d0d3) in spinal cord. Foxm1 and its transcriptional targets are significantly upregulated only in the spinal cord at 3dpa, but not in the whole tail ( Figure 1D).…”

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Foxm1 regulates neuronal progenitor fate during spinal cord regeneration

Pelzer¹,

Phipps

Thuret³

et al. 2020

Preprint

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Keywords: spinal cord / regeneration / Foxm1 / progenitor / Xenopus / differentiation Pelzer et al. Role of Foxm1 during spinal cord regeneration 2 Summary Mammals have limited tissue regeneration capabilities, particularly in the case of the central nervous system. Spinal cord injuries are often irreversible and lead to the loss of motor and sensory function below the site of the damage [1]. In contrast, amphibians suchas Xenopus tadpoles can regenerate a fully functional tail, including their spinal cord, following amputation [2,3]. A hallmark of spinal cord regeneration is the re-activation of Sox2/3+ progenitor cells to promote regrowth of the spinal cord and the generation of new neurons [4,5]. In axolotls, this increase in proliferation is tightly regulated as progenitors switch from a neurogenic to a proliferative division via the planar polarity pathway (PCP) [6][7][8]. How the balance between self-renewal and differentiation is controlled during regeneration is not well understood. Here, we took an unbiased approach to identify regulators of the cell cycle expressed specifically in X.tropicalis spinal cord after tail amputation by RNAseq. This led to the identification of Foxm1 as a potential key transcription factor for spinal cord regeneration. Foxm1-/-X.tropicalis tadpoles develop normally but cannot regenerate their spinal cords. Using single cell RNAseq and immunolabelling, we show that foxm1+ cells in the regenerating spinal cord undergo a transient but dramatic change in the relative length of the different phases of the cell cycle, suggesting a change in their ability to differentiate. Indeed, we show that Foxm1 does not regulate the rate of progenitor proliferation but is required for neuronal differentiation leading to successful spinal cord regeneration. Pelzer et al. Role of Foxm1 during spinal cord regeneration 3 Results Foxm1 is specifically expressed in the regenerating spinal cordWe compared the transcriptome of isolated spinal cords at 1day post amputation (1dpa) and 3dpa to spinal cord from intact tails (0dpa, Figure 1A). Principle component plot, dendogram of sample-to-sample distances and MA-plot of the log fold change (FC) of expression in relation to the average count confirmed the quality of the data (Figures S1A-D). Between 0dpa and 1dpa, 5129 differentially expressed (DE) transcripts (FC> 2 and FDR<0.01) were identified (2074 down-, 3055 up-regulated). Between 0dpa and 3dpa, 9787 genes are differentially expressed (4609 down and 5178 up-regulated, Figure S1E).To identify the most enriched biological processes by gene ontology (GO), a nonbiased hierarchical cluster for all DE genes was performed ( Figure 1B). We observed three phases: first an increase in expression of genes involved in metabolic processes (cluster I), then a strong upregulation of genes associated with cell cycle regulation (cluster II and III) and finally, a downregulation of expression of genes involved in nervous system development (Cluster IV and V, Figure 1B).Using Ingenuity Pathway Analysis (IPA), we identi...

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Transcriptional dynamics of tail regeneration in Xenopus tropicalis

Cited by 27 publications

References 28 publications

Model systems for regeneration: Xenopus

Model systems for regeneration: Xenopus

An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity

Foxm1 regulates neuronal progenitor fate during spinal cord regeneration

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