Morphogenetic Signaling

Team Leader
Shigeo Hayashi (Ph.D. )

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).

Select References

Miao G , Escargot controls the sequential specification of two tracheal tip cell types by suppressing FGF signaling in Drosophila. Development. 2016 Oct 14. doi: 10.1242/dev.133322

Otani.T , IKKε inhibits PKC to promote Fascin-dependent actin bundling. Development. 2016 Oct 15. doi: 10.1242/dev.138495

Kagayaki Kato, Bo Dong, Microtubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion. Nature Communications. 2016 Apr 12. doi: 10.1038/ncomms11141

Otani T, et al. A transport and retention mechanism for the sustained distal localization of Spn-F-IKKepsilon during Drosophila bristle elongation. Development 142.2338-51 (2015)

Hannezo E, et al. Cortical instability drives periodic supracellular actin pattern formation in epithelial tubes. Proc Natl Acad Sci U S A (2015)

Dong B, et al. A fat body-derived apical extracellular matrix enzyme is transported to the tracheal lumen and is required for tube morphogenesis in Drosophila. Development 141.4104-9 (2014)

Miao G and Hayashi S. Manipulation of gene expression by infrared laser heat shock and its application to the study of tracheal development in Drosophila. Dev Dyn 244.479-87 (2015)

Dong B, et al. Balance between Apical Membrane Growth and Luminal Matrix Resistance Determines Epithelial Tubule Shape. Cell Rep (2014)

Niwa N, et al. Homeogenetic inductive mechanism of segmentation in polychaete tail regeneration. Dev Biol (2013)

Dong B, et al. Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control. Nat Commun 4.1358 (2013)

Kondo T. and Hayashi S. Mitotic cell rounding accelerates epithelial invagination. Nature (2013)

Otani T, et al. IKKepsilon Regulates Cell Elongation through Recycling Endosome Shuttling. Dev Cell 20.219-32 (2011)

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Lab Homepage



Drosophila embryo at the beginning of tracheal placed invagination (magenta). Cell outline is labeled green.
Formation of new organ primodia 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 outside of the epithelia and invaginate inwardly. 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. Lumen is filled with apical extracellular matrix (magenta). Apical membrane is labeled wit cyan and basement membrane is labeled green. Tube 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).