Members
Principal Investigators #
Noriko Funayama (Kyoto University) #
Research Theme: The mechanism of sponge skeleton formation, where cells produce, transport, and connect siliceous spicules.
The sponge body is supported by a skeleton constructed from numerous microscopic glass needles (spicules) assembled in three dimensions, which determines the overall body shape. To elucidate the principles of this skeleton formation, Funayama conducted live-imaging analysis and cell identification of the spicules. The results revealed that the processes of spicule manufacturing, transportation/placement, and construction/joining are carried out in a flow-like manner by cells with limited individual functions, much like a human construction project. This cellular construction work is completely different from the conventional concept of morphogenesis where “cells stack up like blocks to form a shape,” leading to the proposal of a new concept in developmental biology. This research aims to analyze the detailed behavior of each cell, much of which remains a mystery, and to elucidate the molecular mechanisms that enable this coordinated “construction work.” Furthermore, through collaborative research with Akiyama (mathematics) and Kondo (experiments, fish fins), this study will pursue “how diverse a range of forms can be created” by this novel morphogenetic mechanism and “whether cells in higher organisms possess the same functions.”
Shigeru Kondo (Osaka University) #
Research Theme: The formation of fish fins through the assembly of collagen needle-like crystals.
In the late stages of animal development, organs much larger than the cellular scale are formed with precision. However, cells are physically fragile and cannot alone provide the mechanical support necessary for organ construction. Therefore, in late-stage development, “bones” (exoskeletons and endoskeletons) play a major role in morphogenesis, yet the principles by which cells create the “shape” of bones are almost entirely unknown. The tips of zebrafish fins are densely packed with long (up to 300 µm) collagen rod-like crystals called actinotrichia, which act as a scaffold to physically maintain the shape of the fin tips. Further inward, the actinotrichia are bundled at regular intervals, and osteoblasts perform ossification there, creating the bone pattern. We have already discovered that three types of fin cells (basal epithelial cells, mesenchymal cells, and osteoblasts) use actinotrichia as “building materials” in a division-of-labor system to create, align, and ossify them, thereby forming the fin bone pattern. This research aims to achieve a complete understanding of this process, reproduce it in vitro, and reconstruct it in silico through computer simulations. The goal is to establish a new concept for previously unexplained late-stage morphogenetic phenomena and to lay the foundation for future regenerative medicine.
Teruyuki Niimi (National Institute for Basic Biology) #
Co-Investigator: Hiroki Gotoh (Shizuoka University) #
Research Theme: Elucidation of three-dimensional morphogenesis through “folding and unfolding.”
The bodies of arthropods are covered by an exoskeleton composed of chitin fibers and proteins secreted by epidermal cells. This exoskeleton is highly rigid, providing excellent defense, but it lacks elasticity and malleability. Therefore, during growth, it is replaced with a larger one through molting. The new exoskeleton is formed in a “compactly folded” state inside the old one. The unfolding of these folds causes an expansion in size and a “transformation” dependent on the folding pattern. A classic example is the rhinoceros beetle’s horn. The new exoskeleton that forms the horn (the horn primordium) is stored in a very densely folded state within the larval head. This primordium inflates in a short time during pupation, and a huge horn emerges. In other words, the external morphology is encoded as the folding pattern of the new exoskeleton. This research will clarify, at the cellular and molecular levels, how the core folding structures of this developmental style are created, using the rhinoceros beetle as a research subject. Additionally, by analyzing the horns of treehoppers, which create diverse forms, we aim to derive general principles connecting folding and 3D morphology and demonstrate that this principle can be used to create arbitrary 3D structures.
Shizue Osawa (Nagoya University) #
Co-Investigator: Reiko Tajiri (Chiba University) #
Research Theme: ECM remodeling that constructs insect exoskeleton morphology and its molecular mechanisms.
Many exoskeleton-bearing organisms create a new exoskeleton in a folded state before molting and then unfold it afterward. During this process, the body expands and transforms simultaneously, with the transformation depending on the folding pattern. In other words, the morphogenesis of the exoskeleton is not a continuous, gradual process like that in vertebrates, but an “integral molding by folding pattern” method. Since this method of morphogenesis differs greatly from the principles of early embryonic development, its details are still largely unknown. To elucidate this, a wide range of knowledge is required, from the macro-level (elucidating the relationship between folding and 3D morphology) to the micro-level (behavior of epithelial cells, properties of the cuticle, gene functions). Using Drosophila, which is advantageous for molecular genetic analysis and live imaging, our research group will focus primarily on the micro-level to analyze the molecular regulatory mechanisms of fold formation and unfolding. By integrating our findings with the research of the Niimi group, which mainly focuses on macro-level analysis, and combining them with mathematical models, our ultimate goal is to clarify the fundamental laws of “integral molding by folding.”
Takeshi Onuma (Kagoshima University) #
Research Theme: 3D construction of a house using animal fibers secreted by the epidermis.
Larvaceans (Oikopleura) live inside a “house” made of a cellulose membrane. This house has a complex structure with ducts and filters arranged to collect and filter plankton. How this house is made is a complete mystery, and the purpose of this research is to uncover it. The house is disposable, and the larvacean replaces it with a new one several times a day. A spare, compactly folded house is held in a state of 2-3 stacked layers, and the outermost one inflates in just a few minutes to become the new house. Since the house contains no cells, something must be creating this complex structure. However, the approximately 2,400 epidermal cells that secrete cellulose are arranged in a flat plane, so there is no “mold” for creating the complex 3D structure. We have been studying the morphogenesis of larvaceans to solve this mysterious manufacturing principle and have recently found a clue. Electron microscopy reveals that the house is a woven fabric of cellulose fibers, and differences in weaving create the functions of each part. Furthermore, dynamic changes occur in the weaving method and thread structure during unfolding. From the new perspective of how cells create woven (or knitted) fabrics, we will approach the mystery of house formation. This research is extremely novel from a biological standpoint, and its elucidation could lead to new manufacturing technologies.
Yasuhiro Inoue (Kyoto University) #
Research Theme: The mechanics of folding and unfolding that create biological surface structures.
Since a 3D shape is the form created by an object’s surface, the morphogenesis of an organ can be described as the shaping of a surface. We have previously contributed to the understanding of morphogenesis from a mechanical perspective by applying a 3D vertex model that describes the deformation of a cell collective’s surface. We have applied the 3D vertex model to the analysis of insect exoskeleton formation, showing that the exoskeleton morphology is stored as folds in the surface of the larval cell collective and that the 3D shape emerges through its physical unfolding (in collaboration with Niimi and Kondo). However, it is still a mystery by what rules insects convert a 3D shape into a folding diagram and by what elementary processes they integrally mold it onto a surface. This research aims to clarify the mechanical principles of “folding and unfolding” that create surface structures, focusing on insect exoskeletons. We will develop the 3D vertex model to establish a simulation platform for analyzing large-scale object deformation at the organ level and tackle the mystery of “conversion to a folding diagram and integral molding onto a surface.”
Masakazu Akiyama (University of Toyama) #
Research Theme: The mathematics of biological construction principles using needle-like materials.
Believing that mathematical models that extract only the essence are effective for understanding complex biological phenomena, I have used the approach of “representing phenomena with mathematical models having the fewest possible variables,” achieving results in collaborative research with experimental researchers. Morphogenesis includes not only the complexity of a biological phenomenon but also the complexity of 3D geometry, which is why representing it with a mathematical model of few variables is effective for understanding it. In this research, we will target the skeletal formation of freshwater sponges and zebrafish fins and create a mathematical model representing the “assembly of highly rigid rod-like (needle-like) materials.” In these systems, simplification is possible by considering that “the materials do not deform” and “the role of cells is to manipulate the materials.” Based on this idea, we will establish a basic mathematical model for the assembly of materials in the freshwater sponge and fin skeleton systems. The phenomenon where highly rigid materials such as collagen and bone form the basis of morphology is highly general, and it is expected that the development of this mathematical model can be applied to a wider range of morphogenetic phenomena.
Shintaro Yamasaki (Waseda University) #
Co-Investigator: Misaki Sakashita (Tokyo University of Science) #
Research Theme: Elucidation of morphogenetic principles through structural optimization and its engineering applications.
Structural optimization is a methodology for creating the optimal morphology of a structure based on mathematical grounds to meet engineering design requirements. When the frame structure of a chair or the electrolyte flow path of a secondary battery is designed using structural optimization, structures similar to bone trabeculae and the water canals of freshwater sponges are obtained, respectively. This suggests that the forms acquired through biological evolution can be understood as the result of some kind of optimization. Focusing on this point, this research aims to mathematically elucidate the forms that organisms take by reproducing the morphogenesis of the organisms studied by the experimental team members through structural optimization. Furthermore, by applying the principles of biological morphogenesis to engineering, we aim to create innovative industrial products, such as inflatable structures with complex internal structures exceeding conventional engineering (applicable to temporary housing) and new 3D printer modeling methods. In collaboration with the experimental team members of this research area, we are already making progress in elucidating the mechanisms of fish vertebrae and larvacean house morphogenesis through structural optimization, and we are well-prepared to advance this research.
Publicly Offered Research Members (2021-2022) #
Hiroshi Nishino (Hokkaido University) #
Research Theme: Elucidation of the construction method of insect auditory ossicles.
Gaku Kumano (Tohoku University) #
Research Theme: Analysis of jellyfish tentacle branching mechanisms through the coordination of chitin and pluripotent stem cells.
Koji Tamura (Tohoku University) #
Research Theme: Methodology for differentially creating rod-shaped and tile-shaped bones within fish fins.
Tetsuya Kojima (The University of Tokyo) #
Research Theme: “Shape” creation in insect limbs through the “Parthenon” construction method and “hollowing” process.
Katsuko Furukawa (The University of Tokyo) #
Research Theme: Tissue structure control by a self-three-dimensionalizing cube model with a nano/micro-textured lattice interface.
Alice Tsuboi (Kyoto University) #
Research Theme: Elucidation of the construction principles of insect eclosion wings based on the extracellular matrix.
Sawako Yamashiro (Kyoto University) #
Research Theme: Visualization and elucidation of microenvironment sensing mechanisms by fluorescence single-molecule imaging.
Kenji Matsuno (Osaka University) #
Research Theme: Research on the physical constraints by the cuticle that straighten the anterior-posterior axis of the embryo.
Mikiko Inaki (Osaka University) #
Research Theme: Elucidation of digestive tract morphogenesis mechanisms through the localized control of non-cellular materials.
Kana Furukawa (Osaka University) #
Research Theme: Who shapes the annular cartilage?
Asako Shindo (Kumamoto University) #
Research Theme: Construction of lumen-cell interactions and spherical aggregates as seen in thyroid morphogenesis.
Koichi Matsuo (Keio University) #
Research Theme: Construction techniques for bilaterally symmetric skeletons using homochiral elements.
Yuki Itakura (RIKEN) #
Research Theme: Shaping of sensory organs through self-organization of molecules in the extracellular space.
Isao Matsuo (Osaka Women’s and Children’s Hospital) #
Research Theme: The uterus that enables high fecundity: Mouse embryo shaping by the decidua filled with extracellular matrix.
Masashi Tachikawa (Kyoto University) #
Research Theme: A mechanodynamic model of artisan cells that manipulate non-cellular materials.
Nen Saito (National Institute for Basic Biology) #
Research Theme: Theoretical study for elucidating 3D morphogenesis shaped by tissue-scale cytoskeletal orientation.
Masaya Yamamoto (Tohoku University) #
Research-Theme: Development of bio-adaptive materials for four-dimensional control of cell aggregates.
Takeo Matsumoto (Nagoya University) #
Research Theme: Building a house in a storm: How do diatoms overcome changes in external forces to grow their bodies?
Takao Yasui (Nagoya University) #
Research Theme: Creation of non-cellular wire structures that generate “lines, surfaces, and spaces” and analysis of cell aggregate behavior.
Yosuke Imai (Kobe University) #
Research Theme: Fluid-structure interaction analysis of thin, time-varying biological building components—A CAE method for body construction.
Publicly Offered Research Members (2023-2024) #
Koji Tamura (Tohoku University) #
Research Theme: Methodology for transforming spinous ray fin bones into special morphologies.
Takahisa Kotake (Saitama University) #
Research Theme: Molecular mechanisms of plant body construction by extracellular proteoglycans.
Hidenori Hashimura (The University of Tokyo) #
Research Theme: Elucidation of the processing method for hardening cellulose in slime mold fruiting body construction.
Tetsuya Kojima (The University of Tokyo) #
Research Theme: The role of the “Parthenon” construction method and “hollowing” process in the “shape” creation of insect limbs.
Takuya Miyata (Nagoya University) #
Research Theme: Wall-strengthening method for the brain primordium that thickens and grows against external pressure: Energy-storing self-binding and root-spreading spacing.
Toshiya Ando (Kyoto University) #
Research Theme: Weevil scale photonic crystal formation by intracellular/extracellular microphase separation.
Sawako Yamashiro (Kyoto University) #
Research Theme: Elucidation of the function of in-vivo hydrodynamic forces by fluorescence single-molecule imaging.
Mikiko Inaki (Osaka University) #
Research Theme: Elucidation of digestive tract morphogenesis mechanisms through the localized control of non-cellular materials.
Kenji Matsuno (Osaka University) #
Research Theme: Research on the physical constraints by the cuticle that straighten the body’s anterior-posterior axis.
Shin Satoh (Okayama University) #
Research Theme: Elucidation of the cellular mechanisms supporting the construction of the “foundation” and “pillars” of axolotl dermal collagen.
Makoto Seiki (Yamaguchi University) #
Research Theme: Body construction by YAP mechano-homeostasis that pushes back when pushed.
Yuki Sato (Kyushu University) #
Research Theme: Amniotic membrane formation mechanism on soft ground—An approach through trans-scale observation.
Tomoyuki Nakamura (Kansai Medical University) #
Research Theme: Molecular mechanisms of assembly and differential production of the extracellular matrix.
Yuki Itakura (RIKEN) #
Research Theme: Formation of olfactory organ surface nanostructures by self-organizing extracellular matrix molecules.
Katsuhiko Sato (Hokkaido University) #
Research Theme: A cortical flow model to clarify the mechanism of collective movement of workers (cells).
Nen Saito (Hiroshima University) #
Research Theme: Mathematical research for elucidating 3D morphogenesis driven by topological defects.
Masashi Tachikawa (Yokohama City University) #
Research Theme: Understanding the manipulation of non-cellular materials as a cooperative phenomenon of cell groups with a mechanical model.
Takeo Matsumoto (Nagoya University) #
Research Theme: Building a house in a storm: Exploring the secrets of how diatoms overcome changes in external forces to form stable morphologies.
Yosuke Imai (Kobe University) #
Research Theme: Fluid-structure interaction analysis of body construction—Development of computational technology connecting post-construction and pre-construction states.
Fujio Tsumori (Kyushu University) #
Research Theme: High-resolution growth patterning of foam materials.