Laboratory for Reconstitutive Developmental Biology [Closed Mar. 2019] | RIKEN BDR

Laboratory for Reconstitutive Developmental Biology

Unit Leader

Miki EbisuyaPh.D.

    [Closed Mar. 2019]

Reconstituting developmental mechanisms to better understand them

Research Summary

In our lab, we strive to create or reconstitute multicellular developmental mechanisms. Our aim of reconstitution is to test the sufficiency of current understandings of mechanisms of interest, as well as to discover unexplained or unexpected elements through observation. The fundamental principles of development include cell autonomous differentiation, spatio-temporal pattern formation and tissue deformation. Thus, we have been trying to reconstitute these principles one by one and so far succeeded in reconstituting cell autonomous differentiation. Namely, we created an artificial gene circuit mimicking Delta-Notch lateral inhibition in mammalian cell culture, causing spontaneous bifurcation of initially identical cells into two different cell types (Matsuda et al, Nat Commun 2015). Now we are working on the reconstitution of reaction-diffusion pattern formation, intercellular synchronized oscillation and 3D-tissue deformation. Artificially reconstituted systems also have the advantage of facilitating measurements and the modification of parameters, which we hope will contribute to the quantitative understanding of developmental principles.

Bifurcation of two daughter cells that were engineered with a synthetic gene circuit into red and green cell types (modified from Matsuda et al, Nat Commun 2015)

A cell colony showing a salt-and-pepper pattern of red cells and green cells (Left: Cells engineered with a synthetic gene circuit, Right: Simulation)

Research Theme

  • Reconstitution of cell autonomous differentiation
  • Reconstitution of cell pattern formation
  • Reconstitution of synchronized oscillation
  • Reconstitution of tissue deformation

Main Publications List

  • Matsuda M, Hayashi H, Garcia-Ojalvo J, et al.
    Species-specific segmentation clock periods are due to differential biochemical reaction speeds.
    Science 369. 1450-1455 (2020) doi: 10.1126/science.aba7668
  • Matsuda M, Yamanaka Y, Uemura M, et al.
    Recapitulating the human segmentation clock with pluripotent stem cells.
    Nature 580. 124–129 (2020) doi: 10.1038/s41586-020-2144-9
  • Sekine R, Shibata T, Ebisuya M.
    Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty.
    Nature communications 9(1). 5456 (2018) doi: 10.1038/s41467-018-07847-x
  • Matsuda M, Koga M, Woltjen K, et al.
    Synthetic lateral inhibition governs cell-type bifurcation with robust ratios.
    Nature Communications 6. 6195 (2015) doi: 10.1038/ncomms7195
  • Imajo M, Ebisuya M, Nishida E.
    Dual role of YAP and TAZ in renewal of the intestinal epithelium.
    Nature Cell Biology 17(1). 7-19 (2015) doi: 10.1038/ncb3084
  • Koga M, Matsuda M, Kawamura T, et al.
    Foxd1 is a mediator and indicator of the cell reprogramming process.
    Nature Communications 5. 3197 (2014) doi: 10.1038/ncomms4197
  • Takashima S, Hirose M, Ogonuki N, et al.
    Regulation of pluripotency in male germline stem cells by Dmrt1.
    Genes and Development 27(18). 1949-1958 (2013) doi: 10.1101/gad.220194.113
  • Matsuda M, Koga M, Nishida E, Ebisuya M.
    Synthetic Signal Propagation Through Direct Cell-Cell Interaction.
    Science Signaling 5(220). ra31 (2012) doi: 10.1126/scisignal.2002764
  • Matsumura S, Hamasaki M, Yamamoto T, et al.
    ABL1 regulates spindle orientation in adherent cells and mammalian skin.
    Nature Communications 3. 626 (2012) doi: 10.1038/ncomms1634
  • Sunadome K, Yamamoto T, Ebisuya M, et al.
    ERK5 Regulates Muscle Cell Fusion through Klf Transcription Factors.
    Developmental Cell 20(2). 192-205 (2011) doi: 10.1016/j.devcel.2010.12.005
  • Mitsushima M, Aoki K, Ebisuya M, et al.
    Revolving movement of a dynamic cluster of actin filaments during mitosis.
    Journal Of Cell Biology 191(3). 453-462 (2010) doi: 10.1083/jcb.201007136
  • Ebisuya M, Yamamoto T, Nakajima M, Nishida E.
    Ripples from neighbouring transcription.
    Nature Cell Biology 10(9). 1106-1113 (2008) doi: 10.1038/ncb1771
  • Yamamoto T, Ebisuya M, Ashida F, et al.
    Continuous ERK activation downregulates anti proliferative genes throughout G1 phase to allow cell-cycle progression.
    Current Biology 16(12). 1171-1182 (2006) doi: 10.1016/j.cub.2006.04.044