A single cell fertilized egg repeated divides and builds up the entire body of an organism. This is called developmental process. There are many aspects of the sequences and functions of genes necessary for this dynamic construction process that we cannot explain with our current knowledge. This is because genes, their products such as RNA and proteins, and cells and tissues interact with each other while harmonizing. I am attempting to find the universal rule(s) in the developmental system common to all hierarchical levels of an organism.
The most fundamental rule in an organism is the central dogma. Information contained in DNA is transcribed to RNA and then translated from the RNA into protein by determining the combination of amino acids and the protein structure. Although all cells on Earth exist based on this simple rule, organisms are surprisingly diverse. The systemic information that supports this diversity is encoded in the genome. It has been found that the number of genes on the actual genome sequence is little different even between nematodes and humans, and that the majority of the genes are well conserved. As such, rather than the mere number of constituents, one of the propelling forces for creating the diversity of species is likely to be control of the relationships between genes, changes in rules of interaction, and feedback between RNA and proteins, which are products of the genes, and changes in the overall network structure. The behavior of cells and tissues is controlled by the coordinated operation of genes. In an organism, systematic interactions take place not only in one single hierarchical level but also among genes, molecules, cells, and tissues and create an order in the entire organism. I am working to solve the mysteries of the developmental process during which an organism takes its shape.
I have approached these questions from two directions. One is disclosure of new information written in the genome. Along with the progress of genome sequencing, the importance of regions that do not encode protein sequences (noncoding regions) has surfaced. In 2007, I discovered that a very short micropeptide consisting of only 11 amino acids is produced from a noncoding region in the genome of Drosophila melanogaster, and that this peptide is indispensable in the embryogenic development of the insect. In 2010, I revealed that the peptide serves as a switch to reverse the reaction of a transcription factor. The study showed an example of a noncoding region, whose significance was unknown at that time, having a biological role, and provided a new approach to understanding the hierarchical levels of the genome.
The other target of research is the mechanisms of morphogenesis during the developmental process. One of most dynamic movements observed during embryonic cleavage and forming tissues and organs is the infolding of epithelium. The epithelium is a sheet-like multicellular tissue formed by cells that are densely joined together. During the process of development, various organs are formed by repeated transformations of the sheet structure. Infolding is one of the morphogenetic movements where the sheet is transformed into a tube. Concerted behaviors of cells at the correct location and timing are key for the correct formation of a multicellular organ, not just the actions of each gene. However, much remains unknown regarding how the behaviors are controlled. I observed the precise behaviors of cells during epithelial infolding of D. melanogaster via live-cell imaging and discovered that the infolding occurred in two stages. A sheet consisting of about 40 cells first sunk slowly and then infolded rapidly. Spheroidization of cells accompanying the mitotic phase was found to be involved in the acceleration. Furthermore, I discovered that infolding was regulated not only by one mechanism but by three mutually compensating mechanisms. These findings became new rules of concerted actions of cells during epithelial infolding.
I will continue actively using technologies such as live-cell imaging and next-generation sequencing as well as mathematical analysis to investigate the systems of development that connect the genome and spontaneous morphogenetic movements in animal embryos. By using the experiences acquired so far and new technologies, I will first make a precise description of the expression states of all genes in the morphogenetic space in an embryo. Based on the data, I will analyze the network of genes comprehensively, rather than by focusing on a specific gene, in order to discover the rules that connect the hierarchical levels of genome, cell, tissue, and organism. My long-term goal is to find the basic rules of development common to all animals based on the studies that use drosophila as the model. Driven by curiosity about the unknown world, I will undertake research to move embryology to the next phase by using old and new technologies. Personal interaction is also indispensable for new research. I’d like to actively construct a network with people from various fields and collaborate with them to conduct interesting studies. I welcome inquiries and visits. Please feel free to contact me if you have interest in these beautiful developmental phenomena.