Laboratory for Morphogenetic Signaling | RIKEN BDR

Laboratory for Morphogenetic Signaling

Team Leader

Shigeo HayashiPh.D.

Photo of principal investigator

  • Location:Kobe / Developmental Biology Buildings
  • E-mail:shigeo.hayashi[at]riken.jpPlease replace [at] with @.
  • Lab Website

Morphogenesis of cell and organ shape

Research Summary

Our research aim is to understand fundamental mechanisms of animal morphogenesis with particular interest in the mechanical basis of tissue movement and its interaction with the extracellular environment. Our main research focus is the tracheal system in the Drosophila embryo, a network of tubular epithelium used as a respiratory organ. Trachea is formed through invagination, tube formation, elongation, fusion, and final maturation into a respiratory organ. We are particularly interested in the mechanical control of epithelial architectures. Epithelium is stabilized by cell-cell adhesion and cell-matrix adhesion. Breaking this stability is essential for initiating morphogenetic movement. We found that prospective tracheal primordium is under negative tension (pressurized). Anisotropic redistribution of tissue tension and timely mitosis initiates local mechanical instability that leads to tissue invagination movement (Kondo and Hayashi, 2013). Once the tracheal network is formed, tube diameter and length are enlarged to reach the final size. Tracheal size change involves increase in cell size, especially an increase in apical cell area facing the luminal side. A key question is how individually controlled cellular growth is coordinated to form coherent tissue architecture. We found that extracellular matrix in the luminal space plays a central role by providing mechanical stability to the tubules (Dong et al., 2013, 2014). Defects in extracellular matrix components lead to destabilization of tube shape and malformation, resulting in tubule morphology seen in organs under pathological conditions.
Another research area of interest is the mechanism of cell morphogenesis. Here we ask the question to what extent single cells can autonomously organize nanometer scale cellular patterns. Our studies have uncovered the role of the cellular trafficking center as an organizer of cell elongation (Otani et al., 2011).

Drosophila embryo at the beginning of tracheal placed invagination (magenta). Cell boundaries are marked green.

Formation of new organ primordia often involves segregation from the epithelial placode by invagination. This picture shows a cross section of the Drosophila tracheal placode. At the center of the placode, tracheal primordial cells (green) constrict apical region facing outer surface of the epithelia and invaginate inward. This process involves a complex interplay of cell boundary tension in the plane of epithelia orchestrated by EGF receptor signaling and inward (basal) movement of cells driving invagination. Cell boundaries are marked with magenta.

Tracheal tubule. Apical membrane (cyan) of cells face the lumen, which is filled with apical extracellular matrix (magenta). Basement membrane is labeled green. Tubule is straight and diameter of the lumen is constant.

Developing mechanosensory bristle precursor cell that elongate up to 400 µm. Elongation is controlled by signaling center at the tip (magenta) and supported by actin bundles (green).

Research Theme

  • Dynamics of epithelial architectures in morphogenesis
  • Control of cytoskeletons in cell morphogenesis

Main Publications List

  • Chu WC, Hayashi S.
    Mechano-chemical enforcement of tendon apical ECM into nano-filaments during Drosophila flight muscle development.
    Current Biology (2021) doi: 10.1016/j.cub.2021.01.010
  • Kondo T, Hayashi S.
    Two-step regulation of trachealess ensures tight coupling of cell fate with morphogenesis in the Drosophila trachea.
    eLife (2019) doi:10.7554/eLife.45145.001
  • Ando T, Sekine S, Inagaki S, et al.
    Nanopore Formation in the Cuticle of an Insect Olfactory Sensillum.
    Current Biology (2019) doi: 10.1016/j.cub.2019.03.043
  • Ogura Y, Wen F, Sami Llano MM, et al.
    A Switch-like Activation Relay of EGFR-ERK Signaling Regulates a Wave of Cellular Contractility For Epithelial Invagination
    Developmental Cell 2018 doi: 10.1016/j.devcel.2018.06.004
  • Miao G and Hayashi S.
    Escargot controls the sequential specification of two tracheal tip cell types by suppressing FGF signaling in Drosophila.
    Development 143. 4261–4271 (2016) doi :10.1242/dev.133322
  • Otani T, Ogura Y, Misaki K, et al.
    IKKepsilon inhibits PKC to promote Fascin-dependent actin bundling.
    Development 143. 3806–3816 (2016) doi:10.1242/dev.138495
  • Kato K, Dong Bo, Wada H, et al.
    Microtubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion.
    Nature Communications 7. 11141 (2016) doi:10.1038/ncomms11141
  • Hannezo E, Dong B, Recho P, et al.
    A cortical instability drives periodic supracellular actin pattern formation in epithelial tubes. Proceedings of National Academy of Sciences of the United States of America 112. 8620–8625 (2015) doi: 10.1073/pnas.1504762112
  • Dong B, Kakihara K, Otani T, et al.
    Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control.
    Nature Communications 4. 1358 (2013) doi:10.1038/ncomms2347
  • Kondo T and Hayashi S.
    Mitotic cell rounding accelerates epithelial invagination.
    Nature 494. 125–129 (2013) doi:10.1038/nature11792

All Publications