ArticleDifferentiation; research in biological diversity2012
Nkx1-2 is a transcriptional repressor and is essential for the activation of Brachyury in P19 mouse embryonal carcinoma cell.
Article in Differentiation; research in biological diversity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 29 citations in OpenAlex.
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- The potent neuroepithelium-promoting activity of Otx2 during gastrulation, as demonstrated by its exogenous epiblast-wide expression in chicken embryos.Frontiers in cell and developmental biology · 2025Article
- The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development.Stem cell reports · 2024Article
- Epigenomic landscape of enhancer elements during Hydra head organizer formation.Epigenetics & chromatin · 2020Article
- Article
- The transcription factor NKX1-2 promotes adipogenesis and may contribute to a balance between adipocyte and osteoblast differentiation.The Journal of biological chemistry · 2019Article
- Early molecular events during retinoic acid induced differentiation of neuromesodermal progenitors.Biology open · 2016Article
- Article
- Neuromesodermal progenitors and the making of the spinal cord.Development (Cambridge, England) · 2015Review
- Integration of signals along orthogonal axes of the vertebrate neural tube controls progenitor competence and increases cell diversity.PLoS biology · 2014Article
- Dullard/Ctdnep1 modulates WNT signalling activity for the formation of primordial germ cells in the mouse embryo.PloS one · 2013Article
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3 authors at 1 institution in 1 country.
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Abstract
Activation of Wnt/β-catenin signaling is crucial for the differentiation of pluripotent stem cells, namely the epiblast, embryonic stem, and embryonal carcinoma cells, into mesendoderm. However, downstream events of Wnt/β-catenin signaling that control the formation of mesendoderm are still unclear. In the present study, we used mouse P19 embryonal carcinoma cells as a model, and identified a homeodomain protein Nkx1-2 as a key regulator of mesendoderm formation. In the mouse embryo, Nkx1-2 was expressed in the primitive streak, in which the nascent mesendoderm emerges. In P19 cells, the expression of Nkx1-2 was activated by Wnt/β-catenin signaling independently of Brachyury, an evolutionary conserved early mesendoderm gene. In contrast, the expression of Nkx1-2 was both necessary and sufficient for the activation of Brachyury. Nkx1-2 acted as a transcriptional repressor to mediate the action of Wnt/β-catenin signaling to activate the Brachyury expression. We found Tcf3 as a potential target of gene repression by Nkx1-2, and the down-regulation of Tcf3 was partly required for effective activation of Brachyury by Wnt/β-catenin signaling. These results suggest that Nkx1-2 is a critical component of the gene regulatory network that operates downstream of Wnt/β-catenin signaling to regulate the formation of mesendoderm.
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