Wnt signalling: variety at the core

Hoppler, Stefan; Kavanagh, Claire

doi:10.1242/jcs.03363

Cited by 240 publications

(247 citation statements)

References 67 publications

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“…This suggests that other T cell-specific factor (tcf) genes, possibly tcf7 (27), can substitute for lef1/tcf1 at later stages of development, as shown in many other sytems (reviewed in ref. 28).…”

Section: Discussionmentioning

confidence: 99%

Innervation is required for sense organ development in the lateral line system of adult zebrafish

Wada

Dambly‐Chaudière

Kawakami

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Superficial mechanosensory organs (neuromasts) distributed over the head and body of fishes and amphibians form the "lateral line" system. During zebrafish adulthood, each neuromast of the body (posterior lateral line system, or PLL) produces "accessory" neuromasts that remain tightly clustered, thereby increasing the total number of PLL neuromasts by a factor of more than 10. This expansion is achieved by a budding process and is accompanied by branches of the afferent nerve that innervates the founder neuromast. Here we show that innervation is essential for the budding process, in complete contrast with the development of the embryonic PLL, where innervation is entirely dispensable. To obtain insight into the molecular mechanisms that underlie the budding process, we focused on the terminal system that develops at the posterior tip of the body and on the caudal fin. In this subset of PLL neuromasts, bud neuromasts form in a reproducible sequence over a few days, much faster than for other PLL neuromasts. We show that wingless/int (Wnt) signaling takes place during, and is required for, the budding process. We also show that the Wnt activator R-spondin is expressed by the axons that innervate budding neuromasts. We propose that the axon triggers Wnt signaling, which itself is involved in the proliferative phase that leads to bud formation. Finally, we show that innervation is required not only for budding, but also for long-term maintenance of all PLL neuromasts.Lgr | post-embryonic development | Thunnus thynnus | Danio rerio

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Section: Discussionmentioning

confidence: 99%

Innervation is required for sense organ development in the lateral line system of adult zebrafish

Wada

Dambly‐Chaudière

Kawakami

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…All members of the Tcf/Lef family (Tcf-1, Tcf-3, Tcf-4 and Lef1) contain an N-terminal binding domain for -catenin, followed by a context-dependent regulatory domain (CRD) with binding sites for the co-repressor Groucho (Gro), a HMG-box DNA-binding domain, and a C-terminal domain with binding sites for the co-repressor Cterminal binding protein (CtBP) [396,397]. Lef1 in general acts as a transcriptional activator in complex with -catenin.…”

Section: The -Catenin Tcf/lef Transcription Complexmentioning

confidence: 99%

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

Voronkov¹,

Krauß²

2012

CPD

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Wnt/ -catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/ -catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, -catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where -catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where -catenin levels are regulated and the nucleus where -catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of -catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellularcatenin levels. However, -catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/ -catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of -catenin at its various locations provides alternative points for therapeutic interventions.

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“…As a consequence, β-catenin is not phosphorylated by GSK3; instead, it translocates into the nucleus, where it binds to target promoters through its interactions with the Tcf proteins. Tcf1 (Tcf7), Lef-1, Tcf3 (Tcf7l1), and Tcf4 (Tcf7l2) form a family of transcription factors that modulate transcription of genes by recruiting chromatin remodeling and histone-modifying complexes to their target genes (6,7). Tcf3 is the most frequently expressed of the Tcf isoforms in ES cells (8) (see Fig.…”

Section: Wnt Pathway | Induced Pluripotent Stem Cell Generationmentioning

confidence: 99%

“…S3A), and it coregulates specific classes of target genes by associating with their promoter regions, along with Oct4, Nanog, and Sox2 (9). Tcf3 has a dual function: It can repress β-catenin target genes by recruiting corepressor factors, and it can activate the same or different classes of genes by interacting with β-catenin and by recruiting different sets of cofactors (6). Interestingly, in gastrulating Xenopus embryos and mammalian cells, on Wnt signaling activation, Tcf3 was shown to be phosphorylated by homeodomain-interacting protein kinase 2 (HIPK2) and to dissociate from target promoters.…”

Section: Wnt Pathway | Induced Pluripotent Stem Cell Generationmentioning

confidence: 99%

T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications

Lluı́s

Ombrato

Pedone

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The heterochromatin barrier must be overcome to generate induced pluripotent stem cells and cell fusion-mediated reprogrammed hybrids. Here, we show that the absence of T-cell factor 3 (Tcf3), a repressor of β-catenin target genes, strikingly and rapidly enhances the efficiency of neural precursor cell (NPC) reprogramming. Remarkably, Tcf3 −/− ES cells showed a genome-wide increase in AcH3 and decrease in H3K9me3 and can reprogram NPCs after fusion greatly. In addition, during reprogramming of NPCs into induced pluripotent stem cells, the silencing of Tcf3 increased AcH3 and decreased the number of H3K9me3-positive heterochromatin foci early and long before reactivation of the endogenous stem cell genes. In conclusion, our data suggest that Tcf3 functions as a repressor of the reprogramming potential of somatic cells.Wnt pathway | induced pluripotent stem cell generation

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Wnt signalling: variety at the core

Cited by 240 publications

References 67 publications

Innervation is required for sense organ development in the lateral line system of adult zebrafish

Innervation is required for sense organ development in the lateral line system of adult zebrafish

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications

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