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Published on: February 16, 2017
Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling
Pedro P Rocha1, Manuela Scholze, Wilfrid Bleiss
1Institute of Medical Genetics, Charité-University Medicine Berlin, Berlin 12200, Germany.
Abstract:
The Mediator complex is commonly seen as a molecular bridge that connects DNA-bound transcription factors to the RNA polymerase II (Pol II) machinery. It is a large complex of 30 subunits that is present in all eukaryotes. The Med12 subunit has been implicated not only in the regulation of Pol II activity, but also in the binding of transcription factors to the bulk of the Mediator complex. We targeted Med12 in mouse embryonic stem cells to investigate the in vivo function of this subunit. We report here the developmental defects of Med12 hypomorphic mutants that have a drastic reduction in Med12 protein levels. These mutants fail to develop beyond embryonic day 10 and have severe defects in neural tube closure, axis elongation, somitogenesis and heart formation. We show that in Med12 hypomorphic embryos, the Wnt/planar cell polarity pathway is disrupted and that canonical Wnt/beta-catenin signaling is impaired. In agreement with this, embryos that are incapable of Med12 expression failed to establish the anterior visceral endoderm or activate brachyury expression, and did not complete gastrulation.
Insights
Med12 protein is crucial for embryonic development, acting as a bridge between transcription factors and RNA polymerase II. Its absence causes severe developmental defects and disrupts key signaling pathways.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- The Mediator complex acts as a molecular bridge linking transcription factors to RNA polymerase II.
- Med12 is a key subunit implicated in regulating transcription and Mediator complex binding.
Purpose of the Study:
- To investigate the in vivo function of the Med12 subunit in mouse embryonic stem cells.
Main Methods:
- Generation and analysis of Med12 hypomorphic mutant mice.
- Assessment of developmental defects and signaling pathway disruptions.
Main Results:
- Med12 hypomorphic mutants exhibit severe developmental defects, failing to survive past embryonic day 10.
- Mutants show defects in neural tube closure, axis elongation, somitogenesis, and heart formation.
- Disruption of Wnt/planar cell polarity and Wnt/beta-catenin signaling pathways observed.
Conclusions:
- Med12 is essential for early embryonic development in mice.
- Med12 plays a critical role in regulating Wnt signaling pathways necessary for gastrulation and organogenesis.
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