At the Board of Directors meeting held at the Hokkaido University Tokyo Office on June 2, 2018, candidates for each award were recommended to the Board of Directors following a rigorous screening by the Selection Committee for Awards. As a result of deliberations by the Zoological Society of Japan Board of Directors, it was decided to confer the 2018 Zoological Society of Japan Awards as follows.<\/p>\n\n\n\n
Zoological Society of Japan<\/p>\n\n\n\n
Member Koji Tamura has advanced highly unique research on the development, regeneration, and evolution of limbs using embryos of chickens, Xenopus laevis, and other organisms. In his research on limb development, he has achieved significant results regarding anteroposterior axis patterning. He demonstrated the mechanism of action of retinoic acid and clarified how shh is expressed in a restricted region at the posterior margin of the limb bud. Furthermore, he has proposed the hypothesis that \"all vertebrates possess the latent capacity to form appendages on the lateral trunk and dorsal midline.\" In his regeneration research, by investigating why Xenopus laevis loses the ability to regenerate limbs upon reaching adulthood, he has challenged to elucidate what capabilities are necessary to regenerate morphologically and functionally complete limbs. Moreover, in his research on limb diversity, he showed that the three digits on the wings of birds possess the identities of digits 1, 2, and 3 out of the typical five digits. In recent years, he identified avian-specific gene expression regulatory regions and proposed an evolutionary scenario for how flight feathers came to be formed on the forelimbs of birds. Through such diverse research on vertebrate limbs, Member Tamura's achievements, which have made a tremendous contribution to the development of zoology, make him well-deserving of the Zoological Society of Japan Award.<\/p>\n\n\n\n
Vertebrate appendages (Note 1) have long been studied extensively as models for morphogenesis for several reasons: they are visually prominent structures along with the head and exhibit the phenotypes of numerous human congenital diseases; they show extremely diverse interspecific morphological variations due to their diverse functions such as walking, flying, swimming, and grasping; and some animals are capable of regenerating these forms.<\/p>\n\n\n\n
In the laboratory to which I belong (the Department of Animal Embryology), research on the morphogenesis of vertebrate appendages has been conducted for nearly 40 years. Its central themes are (1) development, (2) regeneration, and (3) diversity. It is no exaggeration to say that as long as a topic falls within these categories, anything feasible is pursued. Over the past 30-plus years that I have been a member, an extraordinarily wide variety of research has unfolded. Nearly all of this research has been independently carried out by the researchers themselves (mostly students), who conceive the ideas, design the experiments, conduct them, analyze the results, and compile their findings. Much of what I have done over these 30 years is to further classify, organize, and connect each piece of research within the framework of the three categories mentioned above, and to present (speak and write) them as a cohesive story. Of course, I have always provided full support for each research project.<\/p>\n\n\n\n
In this lecture, among such \"comprehensive introduction\" stories, I will talk about the morphogenesis of \"digits.\" Among appendage morphogenesis, digits are a simple yet complex structure composed of multiple identical tissues (bone or cartilage) with different shapes. They serve as an ideal model for pattern formation (patterning), as they provided the experimental basis upon which the concentration gradient model in vertebrates was proposed. Beginning with research into the mechanism of action of retinoic acid\u2014a molecule identified in 1987 as functioning as a morphogen (Note 2) for the first time in vertebrates\u2014this story covers the subsequent rejection of the retinoic acid morphogen hypothesis, the complete overshadowing of this work by others, and the eventual identification of the true morphogen.Mario<\/em>The story progresses to the discovery, finger identity revealed through transplantation experiments, and embryological support for the dinosaurian origin of birds. Furthermore, triggered by the success in embryologically viewing birds as descendants of dinosaurs, the research expands into comparative genomic studies exploring the question, \"What is a bird?\"<\/p>\n\n\n\n Due to time constraints, I cannot introduce all the research that has been conducted in this lecture, and I will not touch upon other stories related to diversity research (such as research on the fin-to-limb transition, the competent stripe determining limb position and tissue interactions), content regarding limb regeneration using Xenopus, or the few studies conducted on things other than limbs (such as cardiac morphogenesis)\u2014my apologies to those who have been involved in these studies. However, the system of research is fundamentally the same: each person researches what they find interesting and somehow shapes it (into content presentable in public). We have continued this repetition focusing on the theme of \"Vertebrate Appendage Development, Regeneration, and Evolution.\" I hope to talk about a part of this accumulated work, its current state, and future prospects.<\/p>\n\n\n\n (Note 1) Appendages broadly refer to locomotion organs possessed by animals, but in vertebrates, their unique locomotion organs, \"limbs\" and \"fins,\" are called appendages.<\/p>\n\n\n\n (Note 2) Also known as Katahara. Among morphogenetic molecules responsible for positional information, a molecule that uses a concentration gradient to determine multiple cell differentiation directions at once.<\/p>\n\n\n\n \u3000<\/p>\n\n\n\n Member Yutaka Sato comprehensively elucidated the gene regulatory network in the embryogenesis of the ascidian *Ciona intestinalis*, which belongs to chordates. The ascidian genome was sequenced at a very early stage\u2014the seventh among animals\u2014and he made a major contribution to it, while also working hard on its subsequent refinement and database maintenance. Furthermore, he listed transcription factors and signaling molecules and analyzed all of them, successfully becoming the first in the world to elucidate the genome-wide gene regulatory network in early ascidian embryos. This has been highly praised for its comprehensiveness, as well as its originality and pioneering nature of being analyzed at the cellular level. In addition, through individual gene function analyses, he has achieved results showing a broad expansion into various fields. He has achieved results that significantly advance the understanding of the reasons why gene arrangement on the genome is maintained during the evolutionary process, and has also revealed important findings on the ectoderm fate determination mechanism and the mechanism by which maternal factors in the egg create gene expression patterns after fertilization. Thus, leading the research on the overall picture and structural analysis of the gene expression regulatory network system in early development, Member Yutaka Sato's achievements, which have made a tremendous contribution to the advancement of the field of embryology, make him highly deserving of the Zoological Science Award.<\/p>\n\n\n\n It is said that genome decoding has brought about a major revolution in biology, and having the opportunity to be involved in the sea squirt genome project right after getting a job was an extremely valuable experience. Although it was a time that could be called the dawn of the genomics era, I remember a new world of biology, different from the world I was familiar with as a student, opening up before my eyes. I am glad to see that the sea squirt genome sequence (Kyoto-Hoya assembly), which was updated a few years later, is still actively used worldwide 10 years later.<\/p>\n\n\n\n Sea squirts are chordates belonging to the urochordates (tunicates), which are the sister group to vertebrates, yet their genomes are simpler and more compact than those of vertebrates. Additionally, the number of cells making up the embryo is small, allowing gene expression to be tracked at the single-cell level. Taking advantage of these strengths, efforts have been made to track changes in gene expression for each cell during sea squirt development and to systematically understand the causal relationships. Specifically, work has been done to elucidate regulatory relationships (i.e., gene regulatory networks) through the comprehensive identification of regulatory gene expression patterns at the cellular level and comprehensive knockdown analyses of expressed regulatory genes. Of course, as the culmination of results from research groups around the world studying sea squirt embryo gene expression, it is now possible to systematically explain the question of when, in which cells, through what regulation, and which genes are expressed during sea squirt embryonic development. I am glad to have contributed to this elucidation.<\/p>\n\n\n\n Most temporal and spatial changes in gene expression in ascidian embryos can be explained without contradiction by considering them as binary states of presence or absence of expression, without taking into account quantitative changes in regulatory factors. This is an important feature of the gene regulatory network in ascidian embryos. For example, all gene expression events occurring at the 32-cell stage can be described as Boolean functions represented solely by the presence or absence of regulatory factors. In other words, changes in gene expression in the embryo can be expressed as very simple mathematical formulas. Furthermore, by considering this gene regulatory network as a fate-determination system and analyzing the network mathematically, it is revealed that this network can be regulated by the activities of just five genes. Indeed, by experimentally manipulating the activities of these five genes, various cell types could be created. This, in turn, suggests that the experimentally determined network structure correctly encompasses the fate-determination system of the ascidian embryo.<\/p>\n\n\n\n Tunicates are urochordates, which are the sister group to vertebrates. By elucidating the gene regulatory networks of tunicates, we believe it is possible to clarify the network changes that occurred in chordate evolution, and we are advancing our research in that direction as well. For example, it was previously thought that FGF alone was necessary for neural induction in tunicate embryos, and that BMP signaling was not involved. However, BMP signaling actually negatively regulates neural induction, just as it does in vertebrates. Interestingly, BMP signaling, which is involved in dorsoventral axis determination, is used at different times and in different places. While the vertebrate gastrula organizer plays a role in both dorsoventral axis determination and neural induction, these two processes may have originally been able to function independently. Taking advantage of the simplicity of both the tunicate embryo and its genome, and utilizing its phylogenetic position, we aim to unravel gene expression in development and genomic changes in evolution one by one from the perspective of gene networks.<\/p>\n\n\n\n \u3000<\/p>\n\n\n\n
\n\n\n\nYutaka Sato
Associate Professor, Department of Biological Sciences, Graduate School of Science, Kyoto University
Study on Genome-Based Gene Regulatory Networks in Ascidian Embryonic Development<\/h4>\n\n\n\nReason for the award<\/h5>\n\n\n\n
Winner Summary<\/h5>\n\n\n\n
\n\n\n\nDecember 9, 2018: Academic Award Winner Lectures at the Alternative Event for the Annual Conference<\/h6>\n\n\n\n