Abstract:

An important characteristic of development is its correctness. Recent studies have shown that developmental processes are often accompanied by fluctuations and errors; nevertheless, embryos consistently form their structures accurately. How do embryos achieve correct development despite these challenges? Studies on preimplantation development have uncovered several mechanisms [1]. During this stage, embryos form a cyst-like structure called the blastocyst, which comprises three cell types that arise through two rounds of cell differentiation. Initially, the embryos differentiate into trophectoderm and inner cell mass (ICM), with the ICM subsequently differentiating into epiblast (EPI) and primitive endoderm. Our research on Hippo signaling has demonstrated that it regulates trophectoderm fate specification and pluripotency factor expression during EPI formation [2-4]. Notably, during EPI formation from the ICM, both Hippo signaling and pluripotency factor expression vary among cells. Cells with weaker gene expression are eliminated through a process called cell competition, resulting in the formation of a high-quality EPI [4].

In this seminar, I will introduce and discuss our recent progress on the following questions: (1) The cell fate specification from ICM to EPI occurs asynchronously [5]. Is Hippo signaling involved in EPI fate specification, and how do EPI cells differentiate properly under conditions of asynchronous differentiation? (2) What mechanisms govern cell competition during EPI formation, and what kinds of cells are eliminated? (3) What role does cell competition play during embryogenesis?

References:

1. Plusa, B., Piliszek, A., 2020. Common principles of early mammalian embryo self-organisation. Development 147:dev183079
2. Nishioka, N. et al, 2009. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell 16, 398-410.
3. Hirate, Y. et al, 2013. Polarity-Dependent Distribution of Angiomotin Localizes Hippo Signaling in Preimplantation Embryos. Curr Biol 23, 1181-1194.
4. Hashimoto, M., Sasaki, H., 2019. Epiblast Formation by TEAD-YAP-Dependent Expression of Pluripotency Factors and Competitive Elimination of Unspecified Cells. Dev Cell 50, 139-154 e135.
5. Saiz, N.et al, 2016. Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst. Nat Commun 7, 13463.

担当分野：　分子薬理学講座　諸石（5180)