FY2018 Annual Report

Evolutionary Neurobiology Unit
Assistant Professor Hiroshi Watanabe


It remains largely obscure how the nervous system became functional during early phase of animal evolution. In order to understand molecular and physiological characteristics of the ancestral nervous system, we are analyzing genetic, proteomic and metabolomic features of nervous systems of the extant early-branching animal lineages including poriferans, placozoans, ctenophores, and cnidarians (Figure 1) We designed a systematic approach using cutting-edge experimental techniques (omics, genetics, and imaging) powered by informatics technologies.

Figure 1. Phylogenetic relationship of metazoans. Choanoflagellata as the outgroup.


1. Staff

  • Dr. Hiroshi Watanabe, Assistant Professor
  • Dr. Eisuke Hayakawa, Group Leader
  • Dr. Mei Fang Lin, Postdoctoral Scholar
  • Dr. Ryo Nakamura, Postdoctoral Scholar
  • Amol Dahal, Research Unit Technician
  • Erina Kawai, Research Unit Technician
  • Ryotaro Nakamura, Research Unit Technician
  • Chihiro Kawano, Research Unit Technician
  • Rio Zako, Research Assistant
  • Ivan Mbogo, PhD Student
  • Larisa Scheloukhova, PhD Student
  • Osamu Horiguchi, PhD Student
  • Christine Guzman, PhD Student
  • Jeric Da-noy, Internship Student (September–December 2018)
  • Minato Miyake, Internship Student (Ferbruary–April 2019)
  • Chihiro Arasaki, Reseaerch Unit Administrator

Past members

  • Dr. Shinya Komoto, Staff Scientist (October 2016–March 2018)


2. Collaborations

2.1 Establishment of gene introduction method in marine invertebrates

  • Type of collaboration: Joint research
  • Researchers:
    • Professor Bam, University of Yamanashi


3. Activities and Findings

3.1 Origin and Early Evolutionary Processes of the Nervous System(s).

In 2018, we performed detailed analysis of neural genes in genomes/transcriptomes of the early-branching species. This included comparison of gene sequences, domain organizations, 3D structures and genetic repertoires. We have so far studied genes for 1) transcription factors that play pivotal roles in neurogenesis, 2) enzymes synthesizing/degrading neurotransmitters/neuromodulators, and 3) component proteins of pre-synaptic and post-synaptic macromolecular complexes (Figure 2).



Figure 2.  Left: Predicted three-dimentional structure of a pre-synaptic protein. Right: Phylogenetic analysis of the pre-synaptic protein generated using structure-based sequence alignments. The establishment of a functional synapse is mediated by various cell adhesion proteins that are specifically localized to the synapse. There is a number of core pre-synaptic cell adhesion proteins that bear essential roles in synapse assembly, maturation, transmission, function, and plasticity in bilaterian animals. However, the their ancestral functions in early-branching (or ‘basal’) animals has not been studied in detail.

3.2 Systematic Peptidomics of the Basal Animals

Peptides are widely utilized as intercellular signaling molecules, such as neuropeptides and peptide hormones, not only in Bilateria but also Cnidaria. Despite their essential roles in neurotransmission and neuromodulation in a wide variety of animal lineages, our knowledge of neuropeptides is still quite limited especially in early branching animals mainly due to difficulties of neuropeptide prediction from genome/transcriptome data. In 2018, we continued to work on establishment of analytical system (systematic peptidomics) for highly sensitive peptide identification. Peptidomics, an analytical workflow for identification of naturally occurring short peptides, has been widely used to study peptides in a wide variety of biological matrices. However, sensitive and reliable identifications for short peptides are still difficult even with recent mass spectrometry instruments because large search space has to be scanned due to the lack of a cleavage enzyme specification during the search. We developed a pipeline to improve the sensitivity of short peptide identification and applied this approach to a search for neuropeptides of an cnidarian model Nematostella vectensis (Figure 3).

Figure 3


4. Publications

4.1 Journals

  1. Torata N, Kubo M, Miura D, Ohuchida K, Mizuuchi Y, Fujimura Y, Hayakawa E, Kai M, Oda Y, Mizumoto K, Hashizume M, Nakamura M. Visualizing Energy Charge in Breast Carcinoma Tissues by MALDI Mass-spectrometry Imaging Profiles of Low-molecular-weight Metabolites. Anticancer Res. doi: 10.21873/anticanres.12723. (2018)

  2. Irie M, Hayakawa E, Fujimura Y, Honda Y, Setoyama D, Wariishi H, Hyodo F, Miura D.  Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury. Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2018.01.012. (2018)

  3. Guzman C, Shinzato C, Lu TM, and Conaco C. Transcriptome analysis of the reef-building octocoral, Heliopora coerulea. Scientific Reports. 8, 8397 (2018)

  4. Guzman C, Han X, Shoguchi E, and Nic Chormaic S. Fluorescence from a single Symbiodinium cell. Methods Appl. Fluoresc. IOPscience. 6, 035003 (2018).

  5. Shoemark, DK., Adams, JC., Ziegler, B., Strompen, J., Özbek, S., Watanabe, H., Tucker, RP., Emergence of a Thrombospondin Superfamily at the Origin of Metazoans, Molecular Biology and Evolution, doi: 10.1093/molbev/msz060 (2019)

4.2 Books and other one-time publications

  1. 渡邉寛 (Watanabe, H.)(分担執筆:第2章「脳の起源︱中枢神経系の誕生」遺伝子から解き明かす脳の不思議な世界 (Mystery world of the brains revealed by genes. – 500 million years of the evolutionary history).  (2018)

4.3 Oral and Poster Presentations​

  1. Hayakawa, E., Kawano, C., and Watanabe, H. A Strategy to Analyze the Spectral Datasets of Unknown Compounds Using Spectral Similarity Network, MSP2018, Osaka, Japan, May 15–18 (2018)

  2. Hayakawa, E., Kawano, C., Watanabe, H., An analytical framework for the exploration of naturally occurring short peptides integrating peptide structure prediction and tandem mass spectrometry, MSP2018, May 15–18 (2018)

  3. Lin, MF., Takahashi, S., Foret, S., Miller, D., Transcriptomic profiles of the tropical corallimorpharian Ricordea yuma (Ricordeidae, Corallimorpharia) after re-infection with homologous and heterologous Symbiodinium clades, 4th Asia Pacific Coral Reef Symposium, Cebu, Philippines, June 4–8 (2018)

  4. Lin MF., Reimer J., Kanda M., Arakaki N., Watanabe H. Cnidairan phylogenomics to understand the eumetazoan evolution, Society for Molecular Biology & Evolution, Yokohama, Japan, July (2018)

  5. Watanabe, H. Development of semi-centralized nervous system of Nematostella, The 89th Annual Meeting of the Zoological Society of Japan, Hokkaido, Japan (2018)

  6. Komoto, S., Nakamura, R., Watanabe, H.Is the Cnidarian SemiCNS Homologous to Bilaterian CNSs?, The 20th Annual Meeting of the Society of Evolutionary Studies, Japan, Tokyo, Japan, August 22–25 (2018)

  7. Hayakawa, E.A strategy to analyze the spectral datasets of unknown compounds using mass spectral similarity network, International Mass Spectrometry Conference 2018, Florence, Italy, August 26–31 (2018)

  8. Hayakawa, E. Interpretation of structure from mass information, Joint Conference on Informatics in Biology and Medicine & Pharmacology 2018, Yamagata, Japan, September 19–21 (2018)

  9. Hayakawa, E.Mass Spectrometry and informatic methods to elucidate natural compounds were introduced, Meta-Omics Workshop in Kyoto 2019, Kyoto, Japan, March 9 (2019)


5. Intellectual Property Rights and Other Specific Achievements

External Fundings

  • Grant-in-Aid for Young Scientists B, Japan Society for the Promotion of Science,"Metabolic analysis of neurotransmitters in schizophrenia by ultrahigh-sensitive IM-MS imaging. (超高感度IM-MSイメージングによる統合失調症の神経伝達物質代謝バランス解析)", Lead PI: Hayakawa, E., Amount: 4.29M Yen, Period: Apr. 2017 – Mar. 2019


6. Meetings and Events

6.1 International Advisory Board of OIST Marine Science Station

Date: September 30, 2018
Venue: OIST Marine Science Station

  1. Nakamura R.
    • Poster presentation
    • Poster title: Genetic Homology of Cnidarian Oral Nervous System (ONS) and Bilaterian Central Nervous System (CNS)
  2. Kawai E.
    • Poster presentation
    • Poster title: Genetic Homology of Cnidarian Oral Nervous System (ONS) and Bilaterian Central Nervous System (CNS)

6.2 Okinawa Marine Science Workshop​

Date: November 19, 2018
Venue: OIST Marine Science Station

  1. Hayawaka, E.
    • Oral Presentation
    • Poster title: Environmental analysis using computational mass spectrometry.
  2. Kawai, E.
    • Poster presentation
    • Poster title: Lab Culture of New Model Animals: A Key Step in EvoDevo Research in Post Genomic Era
  3. Kawano, C
    • Poster presentation
    • Poster title:  A strategy to analyze the mass spectrometry-based datasets of unknown compounds in environmental samples using network informatics


7. Other

Nothing to report.​