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Early embryonic development and embryonic stem (ES) cells

Dr. Yamanaka’s research is focused on epithelial morphogenesis in early mammalian development and ES cells. The epithelium is a fundamental type of organized tissues, which plays various roles in development and adult homeostasis. Disruption of epithelia underlies the genesis of various diseases including cancer, where disorganization of tissue structures is a hallmark of malignancy and often results in invasion and metastasis. Thus, understanding how an epithelium is generated and maintained will provide the foundation to understand how diseases like cancer are initiated and progress. The early mouse embryo is a useful model to study epithelial morphogenesis in an in vivo 3D environment. Using live imaging techniques and genetics, we are able to analyze dynamic cellular and molecular activities in individual cells during morphogenesis in developing mouse embryos and embryonic stem cells.

1)    Cell polarization and lineage specification in the preimplantation embryo. At the 8-cell stage, each blastomere establishes apico-basal polarity, which is the foundation of epithelial structures. We are studying the molecular mechanisms of cell polarization and how these processes control subsequent lineage specification through controlling the orientation of cell division and gene expression. The early mouse embryo is a useful model to study epithelial morphogenesis in an in vivo 3D environment. Using live imaging techniques and genetics, we are able to analyze dynamic cellular and molecular activities in individual cells in developing mouse embryos.

2)    Morphogenesis in the mouse gastrula embryo. During gastrulation, the mouse embryo dynamically changes its morphology, generates various cell lineages and forms the basic 3D structure from a simple sheet-like structure. Various cellular behaviors are observed, such as epithelial-mesenchymal transition (EMT), cell migration, cell shape change, and cell proliferation.  Currently we are focusing on development of the cardiovascular system in the embryo.

3)   Generation of embryonic stem cells from non-permissive mouse strains and marmosets and developing novel genome manipulation techniques using Zinc Finger Nucleases (ZFNs).

Understanding dynamic cellular activities during morphogenesis in an in vivo 3D space will provide useful insight into development as well as into various diseases including cancer. Dr. Yamanaka’s research will provide fundamental knowledge for in vitro generation of specific cell types and structures from pluripotent stem cells in order to devise future strategies in regenerative medicine and drug screening.