受精卵の細胞分化を調節する新たな仕組み~ウシ胚を用いて明かされる細胞極性に依存しない分化制御~

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2025-04-01 北海道大学

北海道大学大学院農学研究院の川原学准教授らの研究チームは、ウシの初期胚における細胞分化の新たな制御機構を明らかにしました。これまで、マウス胚の研究から、細胞極性の確立が細胞分化を決定すると考えられていましたが、ウシ胚では細胞極性と分化制御が連動していないことが判明しました。具体的には、ウシ胚では16細胞期以降に細胞極性が形成されるものの、分化を誘導するYAP1タンパク質の核内局在は細胞極性に依存していませんでした。さらに、胚を覆う透明帯を除去すると、YAP1の細胞質局在が抑制され、細胞分化制御が破綻することが分かりました。これらの結果から、ウシ初期胚では、細胞極性とは異なるメカニズムで細胞分化が制御されていることが示され、哺乳類の種によって分化制御機構が多様であることが明らかになりました。

<関連情報>

着床前胚におけるYes-associated protein 1の細胞内局在の極性に依存しない制御 Polarization-independent regulation of the subcellular localization of Yes-associated protein 1 during preimplantation development

Shun Saito ∙ Koji Nishiyama ∙ Hanako Bai ∙ Masashi Takahashi ∙ Manabu Kawahara
Journal of Biological Chemistry  Published:March 19, 2025
DOI:https://doi.org/10.1016/j.jbc.2025.108429

受精卵の細胞分化を調節する新たな仕組み~ウシ胚を用いて明かされる細胞極性に依存しない分化制御~

Abstract

Cell polarization is a crucial developmental process that determines cell differentiation in mouse embryos. During this process, an extensively expressed transcriptional regulator, Yes-associated protein 1 (YAP1), is localized either to the cytoplasm or nucleus via HIPPO signaling. In mouse pre-morula embryos, YAP1 is present in the nuclei of all cells. Thereafter, YAP1 is distributed to the nuclei of outer cells or cytoplasm of inner cells, depending on the establishment of cell polarity and morula formation. However, the dynamics of YAP1 localization in other species, including ruminants, remain unclear. To gain an in-depth understanding of cell differentiation in mammalian embryos, we investigated YAP1 localization changes in bovine embryos. Unlike in mouse morulae, YAP1 displayed cytoplasmic localization in most cells, including the outer cells of bovine morulae, after the 32-cell stage. Next, we analyzed the relationship between cell polarity and nuclear localization of YAP1. Polarization of outer cells in the bovine morula began at the late 16-cell stage and was established by the late 32-cell stage, indicating that polarization preceded the nuclear localization of YAP1 in bovine embryos. To explore the regulation of YAP1 localization in bovine morula, we analyzed zona-free embryos and found that the presence of the zona pellucida significantly enhanced YAP1 cytoplasmic localization. Moreover, we observed ectopic expression of SOX2 in zona-free blastocysts, which indicated that cytoplasmic localization of YAP1 was associated with the suppression of pluripotency in the trophectoderm. These findings provide valuable insights into the molecular mechanisms underlying the first cell differentiation in mammalian embryos.

生物工学一般
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