Organismal Patterning

Team Leader
Hiroshi Hamada (M.D., Ph.D.)

My lab studies how left-right asymmetries develop in the mouse embryo. In particular, we focus on two types of cilia that are required for left-right symmetry breaking: rotating cilia that generate leftward fluid flow, and immotile cilia that sense the fluid flow. We also study the role of maternal epigenetic regulators in pre-implantation development. We address these questions by integrating live imaging, structural biology, fluid dynamics and mathematical modeling.

Select References

K Takaoka, Both Nodal signaling and stochasticity select for prospective distal visceral endoderm in mouse embryos. Nat Comm. 2017 Nov 14. doi:10.1038/s41467-017-01625-x

Minegishi K, et al. A Wnt5 activity asymmetry and intercellular signaling polarize node cells for breaking left-right symmetry in the mouse embryo. Dev Cell 40, 439-452 (2017). doi:10.1016/j.devcel.2017.02.010

Shinohara K, et al. Absence of radial spokes in mouse node cilia is required for rotational movement but confers ultrastructural instability as a trade-off. Dev Cell 35, 236–246 (2015). doi:10.1016/j.devcel.2015.10.001

Nakamura T, et al. Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA in the mouse embryo. Nat Commun 3, 1322 (2012). doi:10.1038/ncomms2319

Yoshiba S, et al. Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2. Science 338, 226–231 (2012). doi:10.1126/science.1222538

Shinohara K, et al. Two rotating cilia in the node cavity are sufficient to break left-right symmetry in the mouse embryo. Nat Commun 3, 622 (2012). doi:10.1038/ncomms1624

Takaoka K, et al. Origin and role of distal visceral endoderm, a group of cells that determines anterior-posterior polarity of the mouse embryo. Nat Cell Biol 13, 743–752 (2011). doi:10.1038/ncb2251

Hashimoto M, et al. Planar polarization of node cells determines the rotational axis of node cilia. Nat Cell Biol 12, 170-176 (2010). doi:10.1038/ncb2020

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Three steps that generate left-right asymmetry
Role of motile and immotile cilia in left-right symmetry breaking
Maternal epigenome in early cell specification