ArticlePloS one2013
Dact2 represses PITX2 transcriptional activation and cell proliferation through Wnt/beta-catenin signaling during odontogenesis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Methylation of DACT2 promotes papillary thyroid cancer metastasis by activating Wnt signaling.PloS one · 2014Trial
- miR-200a TargetsAnimals : an open access journal from MDPI · 2025Article
- Genetic requirement ofeLife · 2024Article
- Integrated transcriptomics of human blood vessels defines a spatially controlled niche for early mesenchymal progenitor cells.Developmental cell · 2024Article
- Genetic requirement ofbioRxiv : the preprint server for biology · 2024Article
- Exploring the association between PITX2, third molars agenesis and sella turcica morphology : PITX2, third molars agenesis and sella turcica morphology.Head & face medicine · 2024Article
- The Role of DACT Family Members in Tumorigenesis and Tumor Progression.International journal of biological sciences · 2022Review
- A missense mutation in Pitx2 leads to early-onset glaucoma via NRF2-YAP1 axis.Cell death & disease · 2021Article
- Expression Analysis of the PITX2 Gene and Associations between Its Polymorphisms and Body Size and Carcass Traits in Chickens.Animals : an open access journal from MDPI · 2019Article
- Convergent and divergent genetic changes in the genome of Chinese and European pigs.Scientific reports · 2017Article
- Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma.Journal of biomedical science · 2017Article
- Article
- β-CateninC429S mice exhibit sterility consequent to spatiotemporally sustained Wnt signalling in the internal genitalia.Scientific reports · 2014Article
- Retinoic acid negatively regulates dact3b expression in the hindbrain of zebrafish embryos.Gene expression patterns : GEP · 2014Article
- The cavefish genome reveals candidate genes for eye loss.Nature communications · 2014Article
- PITX2 associates with PTIP-containing histone H3 lysine 4 methyltransferase complex.Biochemical and biophysical research communications · 2014Article
- MSX2 in ameloblast cell fate and activity.Frontiers in physiology · 2014Review
- A model for the molecular underpinnings of tooth defects in Axenfeld-Rieger syndrome.Human molecular genetics · 2014Article
- β catenin in health: A review.Journal of oral and maxillofacial pathology : JOMFPReview
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Dact proteins belong to the Dapper/Frodo protein family and function as cytoplasmic attenuators in Wnt and TGFβ signaling. Previous studies show that Dact1 is a potent Wnt signaling inhibitor by promoting degradation of β-catenin. We report a new mechanism for Dact2 function as an inhibitor of the canonical Wnt signaling pathway by interacting with PITX2. PITX2 is a downstream transcription factor in Wnt/β-catenin signaling, and PITX2 synergizes with Lef-1 to activate downstream genes. Immunohistochemistry verified the expression of Dact2 in the tooth epithelium, which correlated with Pitx2 epithelial expression. Dact2 loss of function and PITX2 gain of function studies reveal a feedback mechanism for controlling Dact2 expression. Pitx2 endogenously activates Dact2 expression and Dact2 feeds back to repress Pitx2 transcriptional activity. A Topflash reporter system was employed showing PITX2 activation of Wnt signaling, which is attenuated by Dact2. Transient transfections demonstrate the inhibitory effect of Dact2 on critical dental epithelial differentiation factors during tooth development. Dact2 significantly inhibits PITX2 activation of the Dlx2 and amelogenin promoters. Multiple lines of evidence conclude the inhibition is achieved by the physical interaction between Dact2 and Pitx2 proteins. The loss of function of Dact2 also reveals increased cell proliferation due to up-regulated Wnt downstream genes, cyclinD1 and cyclinD2. In summary, we have identified a novel role for Dact2 as an inhibitor of the canonical Wnt pathway in embryonic tooth development through its regulation of cell proliferation and differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.