Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway

Fujimi, Takahiko J.; Hatayama, Minoru; Aruga, Jun

doi:10.1016/j.ydbio.2011.10.026

Cited by 53 publications

(64 citation statements)

References 75 publications

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“…The human ZIC2 and Xenopus zic1-5 proteins have recently been shown to act as cofactors that inhibit Wnt-dependent-β-catenin-mediated transcription (Pourebrahim et al, 2011; Fujimi et al, 2012). Upon Wnt stimulation, β-catenin enters the nucleus and interacts with the TCF transcription factors to stimulate transcription of target genes (Behrens et al, 1996).…”

Section: Resultsmentioning

confidence: 99%

A murineZic3transcript with a premature termination codon evades nonsense-mediated decay during axis formation

Ahmed

Ali

Warr

et al. 2013

Disease Models &Amp; Mechanisms

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SUMMARYThe ZIC transcription factors are key mediators of embryonic development and ZIC3 is the gene most commonly associated with situs defects (heterotaxy) in humans. Half of patient ZIC3 mutations introduce a premature termination codon (PTC). In vivo, PTC-containing transcripts might be targeted for nonsense-mediated decay (NMD). NMD efficiency is known to vary greatly between transcripts, tissues and individuals and it is possible that differences in survival of PTC-containing transcripts partially explain the striking phenotypic variability that characterizes ZIC3-associated congenital defects. For example, the PTC-containing transcripts might encode a C-terminally truncated protein that retains partial function or that dominantly interferes with other ZIC family members. Here we describe the katun (Ka) mouse mutant, which harbours a mutation in the Zic3 gene that results in a PTC. At the time of axis formation there is no discernible decrease in this PTC-containing transcript in vivo, indicating that the mammalian Zic3 transcript is relatively insensitive to NMD, prompting the need to re-examine the molecular function of the truncated proteins predicted from human studies and to determine whether the N-terminal portion of ZIC3 possesses dominant-negative capabilities. A combination of in vitro studies and analysis of the Ka phenotype indicate that it is a null allele of Zic3 and that the N-terminal portion of ZIC3 does not encode a dominant-negative molecule. Heterotaxy in patients with PTC-containing ZIC3 transcripts probably arises due to loss of ZIC3 function alone.

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Section: Resultsmentioning

confidence: 99%

A murineZic3transcript with a premature termination codon evades nonsense-mediated decay during axis formation

Ahmed

Ali

Warr

et al. 2013

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…Additionally, Activin signaling repression by follistatin is needed for both head and tail regeneration in planarians [25], suggesting that zic-1 is not a general regulator of that pathway in planarians. Vertebrate Zic2 and Zic3 regulate organizer function by inhibition of Wnt signaling [42], [69]. Additionally, mutations in human zic2 lead to holoprosencephaly [70], a midline defect of the anterior due to perturbed organizer function [43].…”

Section: Discussionmentioning

confidence: 99%

“…Zinc fingers of the cerebellum (Zic) proteins, homologous to Drosophila odd-paired , are conserved in animals, can act as transcription factors, and participate in axis formation, neurogenesis, and mesoderm formation [42]–[49]. However, pleiotropy and redundancy have complicated the identification of specific shared functions for vertebrate Zic genes, and loss-of-function studies have not yet pointed to their common use in only a single signaling pathway [50].…”

Section: Introductionmentioning

confidence: 99%

zic-1 Expression in Planarian Neoblasts after Injury Controls Anterior Pole Regeneration

Vásquez-Doorman

Petersen

2014

PLoS Genet

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Mechanisms that enable injury responses to prompt regenerative outgrowth are not well understood. Planarians can regenerate essentially any tissue removed by wounding, even after decapitation, due to robust regulation of adult pluripotent stem cells of the neoblast population. Formation of pole signaling centers involving Wnt inhibitors or Wnt ligands promotes head or tail regeneration, respectively, and this process requires the use of neoblasts early after injury. We used expression profiling of purified neoblasts to identify factors needed for anterior pole formation. Using this approach, we identified zic-1, a Zic-family transcription factor, as transcriptionally activated in a subpopulation of neoblasts near wound sites early in head regeneration. As head regeneration proceeds, the Wnt inhibitor notum becomes expressed in the newly forming anterior pole in zic-1-expressing cells descended from neoblasts. Inhibition of zic-1 by RNAi resulted in a failure to express notum at the anterior pole and to regenerate a head, but did not affect tail regeneration. Both injury and canonical Wnt signaling inhibition are required for zic-1 expression, and double-RNAi experiments suggest zic-1 inhibits Wnt signaling to allow head regeneration. Analysis of neoblast fate determinants revealed that zic-1 controls specification of notum-expressing cells from foxD-expressing neoblasts to form the anterior pole, which organizes subsequent outgrowth. Specialized differentiation programs may in general underlie injury-dependent formation of tissue organizing centers used for regenerative outgrowth.

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“…The authors found that the only significantly enriched functional ontology class was DNAbinding transcription factors. Interestingly, among these, the Zic family of zinc transcription factors was previously reported to interfere with the Wnt pathway (32). Using a combination of ectopic expression/inactivation of ZICs, and immunoprecipitation experiments in colorectal cancer cell lines or intestinal-crypt derived organoids, the authors showed that ZIC1 and ZIC2 can inhibit the Wnt signaling by physically interacting with the β-catenin/TCF complex (13).…”

Section: Perspectivementioning

confidence: 99%

Polycomb complex PRC1 as gatekeeper of intestinal stem cell identity

Léveillé¹,

Vermeulen²

2016

Stem Cell Investig.

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Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway

Cited by 53 publications

References 75 publications

A murineZic3transcript with a premature termination codon evades nonsense-mediated decay during axis formation

A murineZic3transcript with a premature termination codon evades nonsense-mediated decay during axis formation

zic-1 Expression in Planarian Neoblasts after Injury Controls Anterior Pole Regeneration

Polycomb complex PRC1 as gatekeeper of intestinal stem cell identity

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