|Matsui, Takeshi||Assistant Professor|
|Mizuno, Keiko||Research Support Staff|
|Ichida, Taichi||Research Support Staff|
The ultimate goal of the research in our laboratory is the understanding of totipotency: what defines totipotency and what makes cell totipotent. Germ-line cells, oocyte and sperm, are highly differentiated but nevertheless able to regain totipotency by forming a zygote, thereby initiating embryonic development in the next generation. A prerequisite for understanding totipotency is the knowledge of developmental mechanisms during transition from oocyte to embryo and early embryogenesis. Our current research thus focuses on understanding the principles underlying early mammalian development.
We have so far characterized the following key features:
- Mechanical and structural context plays a key role in morphogenesis and embryonic patterning (Motosugi et al. 2005; Motosugi et al. 2006; Honda et al. 2008)
- An asymmetry may emerge autonomously in an equivalent cellular population with no need for a priori intrinsic differences (Honda et al. 2008)
- Early mouse development involves stochastic processes (Dietrich and Hiiragi 2007; Dietrich and Hiiragi 2008)
These features suggest that, in order to fully understand the mechanisms of early mammalian development, it will be essential to address how the diverse inputs acting on every individual cell are integrated in the embryo at the systems level. We thus adopt a wide variety of experimental approaches in order to understand the development at a molecular, cellular and systems level; in particular, 4D live-imaging, fluorescence-based gene-trap screen, gene expression profiling of individual blastomeres, experimental micromanipulation and computer simulation of the blastocyst morphogenesis. An emerging hypothesis is that early mammalian embryogenesis may be a random and stochastic process in a particular structural context that eventually leads to self-organization. This principle of embryonic patterning may underlie the highly regulative capacity that is unique to mammalian pre-implantation embryos.
At the iCeMS, we are further exploring multi-disciplinary approaches including:
- Characterization of the stochastic patterning process at the meso-scale level. Gene expression profile of individual blastomeres in the mouse pre-implantation embryo will be established by single-cell cDNA amplification, while spatio-temporal gene expression pattern will be visualized by Fluorescence Correlation Spectroscopy (FCS). This collaboration may identify a shift from "stochastic" to "consolidated" pattern of gene expression upon lineage commitment in vivo (Harada lab; CEMI; Saitou lab).
- Potential contribution of cellular geometry to the cell fate specification. Mechanical context will be applied to the embryo or the isolated cell culture using a micro-devise, in order to examine if geometrical information can drive the lineage specification (Chen Lab).
Another research interest is the "epithelial evolution". About 360 million years ago, the first terrestrial vertebrate, amphibians emerged from the water and adapted to life on land. They evolved their surface epithelium into multilayered stratified epithelia. Placing particular emphasis on this epithelium, we intend to uncover the mysteries of the epithelial evolution.
The Hiiragi Lab welcomes all inquiries from graduate students interested in assisting us in our work.
Selected papersMatsui, T., Miyamoto, K., Kubo, A., Kawasaki, H., Ebihara, T., Hata, K., Tanahashi, S., Ichinose, S., Imoto, I., Inazawa, J., Kudoh, J., Amagai, M: SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing. EMBO Mol. Med. 3, 320-333 (2011).
Honda, H., Motosugi, N., Nagai, T., Tanemura, M. and Hiiragi, T. Computer simulation of emerging asymmetry in the mammalian blastocyst. Development 135, 1407-1414 (2008).
Dietrich, J. E. and Hiiragi, T. Stochastic patterning in the mouse pre-implantation embryo. Development 134, 4219-4231 (2007).
|Website||Hiiragi Lab Asst. Prof. Matsui's website|