Induction of canonical Wnt signaling by alsterpaullone is sufficient for oral tissue fate during regeneration and embryogenesis in <i>Nematostella vectensis</i>

Trevino, Michael A.; Stefanik, Derek; Rodríguez, Richard; Harmon, Shane; Burton, Patrick M.

doi:10.1002/dvdy.22774

Cited by 50 publications

(53 citation statements)

References 29 publications

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“…Furthermore, in Hydra, activation of canonical Wnt signaling is sufficient to cause tentacle outgrowth along the body column (Hassel et al, 1993;Broun et al, 2005). By contrast, recent studies in Nematostella show that ectopic activation of canonical Wnt signaling can only induce tentacle and oral fates at the aboral pole of developing animals, not along the body column (Trevino et al, 2011). Additionally, we have demonstrated that Notch signaling is required for tentacle elongation in Nematostella (Fig.…”

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confidence: 52%

Mechanisms of tentacle morphogenesis in the sea anemoneNematostella vectensis

et al. 2013

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SUMMARYEvolution of the capacity to form secondary outgrowths from the principal embryonic axes was a crucial innovation that potentiated the diversification of animal body plans. Precisely how such outgrowths develop in early-branching metazoan species remains poorly understood. Here we demonstrate that three fundamental processes contribute to embryonic tentacle development in the cnidarian Nematostella vectensis. First, a pseudostratified ectodermal placode forms at the oral pole of developing larvae and is transcriptionally patterned into four tentacle buds. Subsequently, Notch signaling-dependent changes in apicobasal epithelial thickness drive elongation of these primordia. In parallel, oriented cell rearrangements revealed by clonal analysis correlate with shaping of the elongating tentacles. Taken together, our results define the mechanism of embryonic appendage development in an early-branching metazoan, and thereby provide a novel foundation for understanding the diversification of body plans during animal evolution.

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confidence: 52%

Mechanisms of tentacle morphogenesis in the sea anemoneNematostella vectensis

et al. 2013

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“…[16][17][18][19] A large number of studies have suggested that WNT signaling is aberrantly activated in GBM and that it promotes GBM growth and invasion via the maintenance of stem cell properties. [20][21][22][23] Here, we will review recent studies from the literature that have described the functions of WNT/β-catenin signaling in development and cancer, with particular emphasis on [24][25][26][27][28][29] genetic and epigenetic alterations that lead to aberrant WNT pathway activation in GBM. We will then discuss the development of therapeutic approaches based on the inhibition of WNT activation and the current status of clinical trials based on agents targeting the WNT pathway.…”

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confidence: 99%

WNT signaling in glioblastoma and therapeutic opportunities

Lee

Ahn

et al. 2016

Laboratory Investigation

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WNTs and their downstream effectors regulate proliferation, death, and migration and cell fate decision. Deregulation of WNT signaling is associated with various cancers including GBM, which is the most malignant primary brain cancer. In this review, we will summarize the experimental evidence supporting oncogenic roles of WNT signaling in GBM and discuss current progress in the targeting of WNT signaling as an anti-cancer approach. In particular, we will focus on (1) genetic and epigenetic alterations that lead to aberrant WNT pathway activation in GBM, (2) WNT-mediated control of GBM stem cell maintenance and invasion, and (3) cross-talk between WNT and other signaling pathways in GBM. We will then review the discovery of agents that can inhibit WNT signaling in preclinical models and the current status of human clinical trials.

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“…Nematostella GSK3-β contained the conserved phosphorylation sites known in Bilateria [6, 50] and its inhibitor alsterpaullone (ALP) is commonly used in Cnidaria, including in Nematostella [32, 33]. Using ALP in the presence of Hg caused a reduction in fos1 and jun1 transcript levels after 1h, suggesting that GSK3-β is an activator of AP-1 transcription in Nematostella (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Anemones were exposed to HgCl 2 at a concentration of 200 µg/L (0.74 µM) in 10 ml medium for 1, 6 and 24 h and compared to control untreated anemones. The kinase inhibitors were reported to display high sequence specificity and are widely used in different organisms including, to some extent, in Nematostella [26, 30-33]; however, their specificity in Nematostella has not yet been established. Kinase inhibitors dissolved in DMSO or only DMSO (control) were added two hours before the introduction of Hg.…”

Section: Methodsmentioning

confidence: 99%

Regulation of AP-1 by MAPK Signaling in Metal-Stressed Sea Anemone

Agron

Brekhman

Morgenstern

et al. 2017

Cell Physiol Biochem

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Background/Aims: AP-1 transcription factor plays a conserved role in the immediate response to stress. Activation of AP-1 members jun and fos is mediated by complex signaling cascades to control cell proliferation and survival. To understand the evolution of this broadly-shared pathway, we studied AP-1 regulation by MAPK signaling in a basal metazoan. Methods: Metal- stressed cnidarian Nematostella vectensis anemones were tested with kinase inhibitors and analyzed for gene expression levels and protein phosphorylation. Results: We show that in cnidarian, AP-1 is regulated differently than in bilaterian models. ERK2 and ERK5, the main MAPK drivers of AP-1 activation in Bilateria, down-regulated fos1 and jun1 transcription in anemones exposed to metal stress, whereas p38 MAPK, triggered transcription of jun1 but not fos1. Furthermore, our results reveal that GSK3-β is the main driver of the immediate stress response in Nematostella. GSK3-β triggered transcription of AP-1 and two other stress-related genes, egr1 and hsp70. Finally, phylogenetic analysis and protein characterization show that while MAPKs and GSK3-β are evolutionarily conserved, Fos and Jun proteins in Nematostella and other cnidarians lack important regulatory and phosphorylation sites found in Bilateria. Conclusion: These findings reveal alternative network interactions of conserved signaling kinases, providing insight into the evolutionary plasticity of immediate stress response mechanisms.

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Induction of canonical Wnt signaling by alsterpaullone is sufficient for oral tissue fate during regeneration and embryogenesis in Nematostella vectensis

Cited by 50 publications

References 29 publications

Mechanisms of tentacle morphogenesis in the sea anemoneNematostella vectensis

Mechanisms of tentacle morphogenesis in the sea anemoneNematostella vectensis

WNT signaling in glioblastoma and therapeutic opportunities

Regulation of AP-1 by MAPK Signaling in Metal-Stressed Sea Anemone

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