Characterization of TGFβ signaling during tail regeneration in the leopard Gecko (<i>Eublepharis macularius</i>)

Gilbert, Richard; Vickaryous, Matthew K.; Viloria-Petit, Alicia

doi:10.1002/dvdy.23977

Cited by 43 publications

(56 citation statements)

References 52 publications

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“…Our results show that p-Smad2 is maximal between 6 h and 48 h, which correlates perfectly with the presence of active TGF-β1. Smad2 phosphorylation has been described in other regenerating organisms, such as Xenopus (Ho and Whitman, 2008) and gecko (Gilbert et al, 2013). In both cases, p-Smad2 is associated with the wound epithelium.…”

Section: Discussionmentioning

confidence: 90%

“…It is possible that Xenopus tadpoles can withstand higher doses than axolotls, and if axolotls could survive at such high concentrations of SB-431542 it might well prevent wound closure as well. Gilbert et al (2013) reported that p-Smad2 is seen throughout tail regeneration in gecko, specifically in the blastema. The authors propose that activation of Smad2 is Activin rather than TGF-β1 related.…”

Section: Discussionmentioning

confidence: 99%

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Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration

et al. 2016

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Axolotls are unique among vertebrates in their ability to regenerate tissues, such as limbs, tail and skin. The axolotl limb is the most studied regenerating structure. The process is well characterized morphologically; however, it is not well understood at the molecular level. We demonstrate that TGF-β1 is highly upregulated during regeneration and that TGF-β signaling is necessary for the regenerative process. We show that the basement membrane is not prematurely formed in animals treated with the TGF-β antagonist SB-431542. More importantly, Smad2 and Smad3 are differentially regulated post-translationally during the preparation phase of limb regeneration. Using specific antagonists for Smad2 and Smad3 we demonstrate that Smad2 is responsible for the action of TGF-β during regeneration, whereas Smad3 is not required. Smad2 target genes (Mmp2 and Mmp9) are inhibited in SB-431542-treated limbs, whereas non-canonical TGF-β targets (e.g. Mmp13) are unaffected. This is the first study to show that Smad2 and Smad3 are differentially regulated during regeneration and places Smad2 at the heart of TGF-β signaling supporting the regenerative process.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration

et al. 2016

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“…3A,B). It has been previously reported that TGFβ signaling is required for multiple events during regeneration of axolotl limbs, Xenopus tadpole tails and Eublepharis tails (Gilbert et al, 2013;Ho and Whitman, 2008;Lévesque et al, 2007). To investigate whether TGFβ is also required during OS regeneration, we treated amputated C. robusta juveniles with 10 μM SB431542, a potent and specific inhibitor of activin receptorlike kinase receptors that mediate TGFβ signal transduction (Mita and Fujiwara, 2007).…”

Section: Requirement Of Tgfβ Signaling During Early Stages Of Regenermentioning

confidence: 96%

“…2A). These two pathways have previously been implicated in the regulation of programmed cell death and proliferation during regeneration (Gilbert et al, 2013;Godwin et al, 2013;Ho and Whitman, 2008;Lévesque et al, 2007;Rao et al, 2009;Stoick-Cooper et al, 2007;Wu et al, 2013). The miRDeep2 program (Friedländer et al, 2012) was used to align and quantify miRNA reads.…”

Section: Differential Expression During Os Regenerationmentioning

confidence: 99%

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

et al. 2017

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Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta, and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed, we also identified 57 novel microRNAs, several of which are among the most highly differentially expressed. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGFβ during early regrowth, and negative regulation of extracellular proteases in late stage regeneration. Consistent with the expression results, we found that inhibition of TGFβ signaling blocked OS regeneration. A correlation network was subsequently inferred for all predicted microRNA-mRNA target pairs expressed during regeneration. Network-based clustering associated transcripts into 22 non-overlapping groups, the functional analysis of which showed enrichment of stress response, signaling pathway and extracellular protease categories that could be related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a role in regulating differentiation and the proliferative state of neural progenitors through regulation of the cytoskeleton and cell cycle.

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“…Though the regenerating tail has a different structure than the original tail, it is an impressive example of regeneration of cartilage, de novo muscle groups, skin, vasculature, and neural ependymal cells (Fisher et al, 2012;Gilbert et al, 2013;Hutchins et al, 2014;McClean & Vickaryous, 2011;Ritzman et al, 2012). While blastema formation is fairly well characterized during limb and fin regeneration in amphibians and teleost fish, lizards follow a different mechanism of regeneration.…”

Section: Regeneration In Lizardsmentioning

confidence: 99%

Reptile genomes open the frontier for comparative analysis of amniote development and regeneration

Tollis

Hutchins

Kusumi³

2014

Int. J. Dev. Biol.

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Developmental genetic studies of vertebrates have focused primarily on zebrafish, frog and mouse models, which have clear application to medicine and well-developed genomic resources. In contrast, reptiles represent the most diverse amniote group, but have only recently begun to gather the attention of genome sequencing efforts. Extant reptilian groups last shared a common ancestor ~280 million years ago and include lepidosaurs, turtles and crocodilians. This phylogenetic diversity is reflected in great morphological and behavioral diversity capturing the attention of biologists interested in mechanisms regulating developmental processes such as somitogenesis and spinal patterning, regeneration, the evolution of "snake-like" morphology, the formation of the unique turtle shell, and the convergent evolution of the four-chambered heart shared by mammals and archosaurs. The complete genome of the first non-avian reptile, the green anole lizard, was published in 2011 and has provided insights into the origin and evolution of amniotes. Since then, the genomes of multiple snakes, turtles, and crocodilians have also been completed. Here we will review the current diversity of available reptile genomes, with an emphasis on their evolutionary relationships, and will highlight how these genomes have and will continue to facilitate research in developmental and regenerative biology.

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Characterization of TGFβ signaling during tail regeneration in the leopard Gecko (Eublepharis macularius)

Cited by 43 publications

References 52 publications

Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration

Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration

A microRNA-mRNA expression network during oral siphon regeneration in Ciona

Reptile genomes open the frontier for comparative analysis of amniote development and regeneration

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