ArticleDevelopmental biology2014
Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst.
Article in Developmental biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 137 citations in OpenAlex.
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- A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation.Nature cell biology · 2025Article
- Mouse trophectoderm stem cells generated with morula signalling inducers capture an early trophectoderm state.Nature cell biology · 2025Article
- From Quiescence to Activation: The Reciprocal Regulation of Ras and Rho Signaling in Hepatic Stellate Cells.Cells · 2025Article
- Signaling pathway regulators in preimplantation embryos.Journal of molecular histology · 2024Review
- Tead4 and Tfap2c generate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification.Nature structural & molecular biology · 2024Article
- Efficient derivation of embryonic stem cells and primordial germ cell-like cells in cattle.The Journal of reproduction and development · 2024Article
- Spatial positioning of preimplantation mouse embryo cells is regulated by mTORC1 and mOpen biology · 2023Article
- Adaptative response to changes in pyruvate metabolism on the epigenetic landscapes and transcriptomics of bovine embryos.Scientific reports · 2023Article
- Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views.Journal of translational medicine · 2023Review
- The surface ectoderm exhibits spatially heterogenous tension that correlates with YAP localisation during spinal neural tube closure in mouse embryos.Cells & development · 2023Article
- Early embryonic lethality of mice lacking POLD2.Molecular reproduction and development · 2023Article
- Trophectoderm formation: regulation of morphogenesis and gene expressions by RHO, ROCK, cell polarity, and HIPPO signaling.Reproduction (Cambridge, England) · 2022Review
- Mechanical regulation of chromatin and transcription.Nature reviews. Genetics · 2022Review
- Rho Kinases in Embryonic Development and Stem Cell Research.Archivum immunologiae et therapiae experimentalis · 2022Review
- Article
- From Mice to Men: Generation of Human Blastocyst-Like StructuresFrontiers in cell and developmental biology · 2022Review
12 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
Funding
Abstract
Specification of the trophectoderm (TE) and inner cell mass (ICM) lineages in the mouse blastocyst correlates with cell position, as TE derives from outer cells whereas ICM from inner cells. Differences in position are reflected by cell polarization and Hippo signaling. Only in outer cells, the apical-basal cell polarity is established, and Hippo signaling is inhibited in such a manner that LATS1 and 2 (LATS1/2) kinases are prevented from phosphorylating YAP, a key transcriptional co-activator of the TE-specifying gene Cdx2. However, the molecular mechanisms that regulate these events are not fully understood. Here, we showed that inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling and disruption of apical-basal polarity. Embryos treated with ROCK inhibitor Y-27632 exhibited elevated expression of ICM marker NANOG and reduced expression of CDX2 at the blastocyst stage. Y-27632-treated embryos failed to accumulate YAP in the nucleus, although it was rescued by concomitant inhibition of LATS1/2. Segregation between apical and basal polarity regulators, namely PARD6B, PRKCZ, SCRIB, and LLGL1, was dampened by Y-27632 treatment, whereas some of the polarization events at the late 8-cell stage such as compaction and apical localization of p-ERM and tyrosinated tubulin occurred normally. Similar abnormalities of Hippo signaling and apical-basal polarization were also observed in embryos that were treated with RHO GTPases inhibitor. These results suggest that RHO-ROCK signaling plays an essential role in regulating Hippo signaling and cell polarization to enable proper specification of the ICM and TE lineages.
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