Daughter cells inherit YAP localization from mother cells in early preimplantation embryos

Abstract

The first stage of cell differentiation during mouse development is the differentiation into the trophectoderm and inner cell mass, which occurs during the 8–32-cell stages of preimplantation embryos. This differentiation is regulated by the Hippo signaling pathway. At the 32-cell stage, embryos establish a position-dependent distribution of the Hippo pathway coactivator, Yes-associated protein 1 (YAP, encoded by Yap1). The outer and inner cells showed nuclear and cytoplasmic localization of YAP, respectively. However, the process by which embryos establish position-dependent YAP localization remains elusive. Here, we established a YAP-reporter mouse line, Yap1^mScarlet, and examined YAP–mScarlet protein dynamics during the 8–32-cell stages using live imaging. During mitosis, YAP–mScarlet diffused throughout the cells. YAP–mScarlet dynamics in daughter cells varied depending on the cell division patterns. YAP–mScarlet localization in daughter cells at the completion of cell division coincided with that in mother cells. Experimental manipulation of YAP–mScarlet localization in mother cells also altered its localization in daughter cells upon completion of cell division. In daughter cells, YAP–mScarlet localization gradually changed to the final pattern. In some divisions during the 8–16-cell stages, the cytoplasmic YAP–mScarlet localization preceded cell internalization. These results suggest that cell position is not a primary determinant of YAP localization and that the Hippo signaling status of the mother cell is inherited by the daughter cells, which likely contributes to the stabilization of the cell fate specification process beyond cell division.