Genetic Interaction of PGE2 and Wnt Signaling Regulates Developmental Specification of Stem Cells and Regeneration

Goessling, Wolfram; North, Trista E.; Loewer, Sabine; Lord, Allegra M.; Lee, Sang; Stoick-Cooper, Cristi L.; Weidinger, Gilbert; Puder, Mark; Daley, George Q.; Moon, Randall T.; Zon, Leonard I.

doi:10.1016/j.cell.2009.01.015

Cited by 641 publications

(657 citation statements)

References 43 publications

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“…Also, WNT proteins regulate the rate of satellite cell proliferation during adult skeletal muscle cell regeneration (Otto et al, 2008). WNT has been shown to have a key role in the initiation of amphibian limb (Kawakami et al, 2006;Yokoyama et al, 2007) and zebrafish fin regeneration (Goessling et al, 2009). Wnt3a has only one highly conserved intronic noncoding SNP in its sequence.…”

Section: Discussionmentioning

confidence: 99%

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

et al. 2014

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External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage. The ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.

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Section: Discussionmentioning

confidence: 99%

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

et al. 2014

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“…111 PGE 2 also has been shown to interact with the Wnt pathway at the level of β-catenin destruction to control HSC formation in vivo. 112 This highlights that caspases are capable of cell repair by modulating the Figure 4 Caspase function in tissue regeneration and tumor cell proliferation. Activation of caspase-3 and -7 during radiotherapy or during tissue injury causes cleavage and activation of iPLA 2 .…”

Section: Caspases In Cell Proliferation and Tissue Regenerationmentioning

confidence: 99%

Old, new and emerging functions of caspases

et al. 2014

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Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.

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“…In mice, cell death-induced regeneration requires the activation of the "Phoenix" pathway, which involves the production of arachidonic acid and prostaglandins 62 . Prostaglandins actually closely interacts with the Wnt pathway to induce stem cell proliferation in mammals 68 and further work will tell us whether similar crosstalk also takes place in non-mammalian regenerative contexts.…”

Section: The Hydra Model Confirms the Link Between Apoptosis--inducedmentioning

confidence: 99%

The Hydra model: disclosing an apoptosis-driven generator of Wnt-based regeneration

Galliot

Chera²

2010

Trends in Cell Biology

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The Hydra model system is well suited to decipher the mechanisms underlying adult regeneration, opening the possibility to characterize those that have been robust enough to be maintained across evolutionary time. The detailed analysis of the activation of the Wnt-βcatenin pathway in bisected Hydra actually shows that the route taken to regenerate a structure as complex as the head dramatically varies according to the amputation level. When decapitation induces a direct redevelopment thanks to Wnt3 signaling from the epithelial cells, head regeneration after midgastric section relies first on Wnt3 signaling from the interstitial cells that undergo apoptosis-induced compensatory proliferation and secondarily activate Wnt3 signaling in the epithelial cells. The relative distribution between stem cells and head progenitor cells is strikingly different in these two contexts indicating that the pre-amputation homeostatic conditions define and constrain the route that bridges wound healing to the re-development program of the missing structure.

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Genetic Interaction of PGE2 and Wnt Signaling Regulates Developmental Specification of Stem Cells and Regeneration

Cited by 641 publications

References 43 publications

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

Old, new and emerging functions of caspases

The Hydra model: disclosing an apoptosis-driven generator of Wnt-based regeneration

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