Details of the Researcher

PHOTO

Misako Okumura
Section
Graduate School of Life Sciences
Job title
Professor
Degree

  • Master (The University of Tokyo)

  • PhD (The University of Tokyo)

e-Rad No.
40806486
Profile
I am interested in the diversity of behavior. Using nematodes as model animals, I have been studying the function, development and evolution of neural circuits that regulate diverse behaviors.

Research History 7

  • 2021/04 - 2026/03
    Hiroshima University　Graduate School of Integrated Sciences for Life, Program of Biomedical Science, Cell Biology Laboratory　Associate Professor

  • 2019/04 - 2021/03
    広島大学大学院　統合生命科学研究科 生命医科学プログラム　助教

  • 2017/04/01 - 2019/03/31
    Hiroshima University　Graduate School of Science　Assistant professor

  • 2016/05/01 - 2017/03/19
    Max Planck Institute for Developmental Biology, Department for Evolutionary Bilolgy　JSPS Overseas Research Fellow

  • 2015/05/20 - 2016/04/30
    Max Planck Institute for Developmental Biology, Department for Evolutionary Biology　Postdoctoral fellow

  • 2015/04/01 - 2015/05/15
    University of Tokyo, Graduate School of Pharmaceutical Sciences　Research fellow

  • 2012/04/01 - 2015/03/31
    University of Tokyo, Graduate School of Pharmaceutical Sciences　JSPS Research Fellow

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Education 4

  • University of Tokyo　Doctoral Program (Department of Pharmaceutical Sciences)　Graduate School of pharmaceutical Sciences

    2012 - 2015

  • University of Tokyo　Master's Program(Department of Pharmaceutical Sciences)　Graduate School of Pharmaceutical Sciences

    2010 - 2012

  • University of Tokyo　Faculty of Pharmaceutical Sciences

    2008 - 2010

  • University of Tokyo　College of Arts and Sciences　Natural Sciences Ⅰ

    2006 - 2008

Committee Memberships 6

  • International Federation of Nematology Societies　IFNS Councillors

    2023 - Present

  • 虫の夕べ オンラインセミナー&交流会　世話人

    2020/11 - Present

  • 15th GfE School and 5th GfE/JSDB young scientist workshop　オーガナイザー

    2025/09 - 2025/09

  • 24th international C. elegans conference　Organizing Committee

    2023/06 - 2023/06

  • 線虫研究の未来を創る会2021　メインオーガナイザー

    2021/08 - 2021/09

  • 23rd International C. elegans Conference　Organizing Committee

    2021/06 - 2021/06

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Professional Memberships 4

  • The Molecular Biology Society of Japan

  • The Japanese Nematological Society

  • The Japan Neuroscience Society

  • Japanese Society of Developmental Biologists

Research Interests 1

  • Phenotypic Plasticity, Nematode, Behavior, Development, Evolution, Light

Research Areas 3

  • Life sciences / Neuroscience - general /

  • Life sciences / Molecular biology /

  • Life sciences / Developmental biology /

Awards 3

  1. Distinguished Researcher

    2024　Hiroshima University

  2. Encouragement Award

    2020　Hiroshima University, Graduate School of Integrated Sciences for Life

  3. Next Leaders Awards

    2018/09/14　Future of the nematodes studies

Papers 31

  1. Characterization of Heat Shock Protein Expression and Its Application to Temporal Gene Expression in the Nematode Pristionchus pacificus Peer-reviewed

    Yuuki Ishita, Hirokuni Hiraga, Takahiro Chihara, Misako Okumura

    Development, Growth & Differentiation　68　e70045　2026/02/15

    DOI： 10.1111/dgd.70045 　

  2. Predatory aggression evolved through adaptations to noradrenergic circuits International-coauthorship Peer-reviewed

    Güniz Göze Eren, Leonard Böger, Marianne Roca, Fumie Hiramatsu, Jun Liu, Luis Alvarez, Desiree L. Goetting, Lewis A. Cockram, Nurit Zorn, Ziduan Han, Misako Okumura, Monika Scholz & James W. Lightfoot

    Nature　2026/01/21

    DOI： 10.1038/s41586-025-10009-x 　

  3. The nematode Pristionchus pacificus requires the Gβ and Gγ proteins for light adaptation but not for light avoidance Peer-reviewed

    Aya Manabe, Keimei Ko, Kenichi Nakayama, Takahiro Chihara, Misako Okumura

    Zoological Science　2025

  4. cGMP-dependent pathway and a GPCR kinase are required for photoresponse in the nematode Pristionchus pacificus Peer-reviewed

    Kenichi Nakayama, Hirokuni Hiraga, Aya Manabe, Takahiro Chihara, Misako Okumura

    PLOS Genetics　2024/11/14

    Publisher: Cold Spring Harbor Laboratory

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    Abstract Light sensing is a critical function in most organisms and is mediated by photoreceptor proteins and phototransduction. Although most nematodes lack eyes, some species exhibit phototaxis. In the nematodeCaenorhabditis elegans, the unique photoreceptor proteinCel-LITE-1, its downstream G proteins, and cyclic GMP (cGMP)-dependent pathways are required for phototransduction. However, the mechanism of light-sensing in other nematodes remains unknown. To address this question, we used the nematodePristionchus pacificus, which was established as a satellite model organism for comparison withC. elegans. Similar toC. elegans, illumination with short-wavelength light induces avoidance behavior inP. pacificus. Opsin, cryptochrome/photolyase, andlite-1were not detected in theP. pacificusgenome using orthology and domain prediction-based analyses. To identify the genes related to phototransduction inP. pacificus, we conducted forward genetic screening for light-avoidance behavior and isolated four light-unresponsive mutants. Whole-genome sequencing and genetic mapping revealed that the cGMP-dependent pathway andPpa-grk-2, which encodes a G protein-coupled receptor kinase (GRK) are required for light avoidance. Although the cGMP-dependent pathway is conserved inC. elegansphototransduction, GRK is not necessary for light avoidance inC. elegans. This suggests similarities and differences in light-sensing mechanisms between the two species. Using a reverse genetics approach, we showed that GABA and glutamate were involved in light avoidance. Through reporter analysis and suppression of synapse transmission, we identified candidate photosensory neurons. These findings advance our understanding of the diversity of phototransduction in nematodes even in the absence of eyes. Author summary Nematodes are a highly diverse group of animals found in a wide variety of habitats and sensory systems. In particular, light-induced behavior has been found to differ among species. The photoreceptor and its downstream pathways inCaenorhabditis eleganshave been identified, revealing unique and distinct characteristics compared to those in other animals. However, the mechanisms of photoreception in other nematodes remain largely unknown. This study focused on the analysis of the photoreception mechanisms inPristionchus pacificus, a species for which many genetic and molecular tools are available. Similar toC. elegans,P. pacificusalso exhibits light avoidance behavior towards short-wavelength light; however, known animal photoreceptor genes could not be identified in theP. pacificusgenome using bioinformatic approaches. Using forward and reverse genetic approaches, we found that certain genes and neurons are required for light avoidance, some of which are conserved inC. elegansphotoreception. These results suggest that the light-sensing mechanisms ofC. elegansandP. pacificusare similar, yet there are differences between the two species. These findings highlight the various light-sensing mechanisms in nematodes.

  5. Co-option of an astacin metalloprotease is associated with an evolutionarily novel feeding morphology in a predatory nematode Peer-reviewed

    Yuuki Ishita, Ageha Onodera, Taisuke Ekino, Takahiro Chihara, Misako Okumura

    Molecular Biology and Evolution　2023/11

    DOI： 10.1093/molbev/msad266 　

  6. Different combinations of serotonin receptors regulate predatory and bacterial feeding behaviors in the nematode Pristionchus pacificus Peer-reviewed

    Yuuki Ishita, Takahiro Chihara, Misako Okumura

    G3:Genes, Genomes, Genetics　11　(2)　jkab011　2021

    DOI： 10.1093/g3journal/jkab011 　

    ISSN： 2160-1836

  7. Screening for CRISPR/Cas9-induced mutations using a co-injection marker in the nematode Pristionchus pacificus. International-journal Peer-reviewed

    Ken-Ichi Nakayama, Yuuki Ishita, Takahiro Chihara, Misako Okumura

    Development genes and evolution　230　(3)　257-264　2020/02/06

    DOI： 10.1007/s00427-020-00651-y 　

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    CRISPR/Cas9 genome-editing methods are used to reveal functions of genes and molecular mechanisms underlying biological processes in many species, including nematodes. In evolutionary biology, the nematode Pristionchus pacificus is a satellite model and has been used to understand interesting phenomena such as phenotypic plasticity and self-recognition. In P. pacificus, CRISPR/Cas9-mediated mutations are induced by microinjecting a guide RNA (gRNA) and Cas9 protein into the gonads. However, mutant screening is laborious and time-consuming due to the absence of visual markers. In this study, we established a Co-CRISPR strategy by using a dominant roller marker in P. pacificus. We found that heterozygous mutations in Ppa-prl-1 induced the roller phenotype, which can be used as an injection marker. After the co-injection of Ppa-prl-1 gRNA, target gRNA, and the Cas9 protein, roller progeny and their siblings were examined using the heteroduplex mobility assay and DNA sequencing. We found that some of the roller and non-roller siblings had mutations at the target site. We used varying Cas9 concentrations and found that a higher concentration of Cas9 did not increase genome-editing events. The Co-CRISPR strategy promotes the screening for genome-editing events and will facilitate the development of new genome-editing methods in P. pacificus.

  8. Serotonin Drives Predatory Feeding Behaviour via Synchronous Feeding Rhythms in the Nematode Pristionchus pacificus Peer-reviewed

    Misako Okumura, Martin Wilecki, Ralf J. Sommer

    G3-GENES GENOMES GENETICS　7　(11)　3745-3755　2017/11

    DOI： 10.1534/g3.117.300263 　

    ISSN： 2160-1836

  9. Linking cell surface receptors to microtubules: tubulin folding cofactor D mediates Dscam functions during neuronal morphogenesis. International-journal Peer-reviewed

    Misako Okumura, Chisako Sakuma, Masayuki Miura, Takahiro Chihara

    The Journal of neuroscience : the official journal of the Society for Neuroscience　35　(5)　1979-90　2015/02/04

    DOI： 10.1523/JNEUROSCI.0973-14.2015 　

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    Formation of functional neural networks requires the coordination of cell surface receptors and downstream signaling cascades, which eventually leads to dynamic remodeling of the cytoskeleton. Although a number of guidance receptors affecting actin cytoskeleton remodeling have been identified, it is relatively unknown how microtubule dynamics are regulated by guidance receptors. We used Drosophila olfactory projection neurons to study the molecular mechanisms of neuronal morphogenesis. Dendrites of each projection neuron target a single glomerulus of ∼50 glomeruli in the antennal lobe, and the axons show stereotypical pattern of terminal arborization. In the course of genetic analysis of the dachsous mutant allele (ds(UAO71)), we identified a mutation in the tubulin folding cofactor D gene (TBCD) as a background mutation. TBCD is one of five tubulin-folding cofactors required for the formation of α- and β-tubulin heterodimers. Single-cell clones of projection neurons homozygous for the TBCD mutation displayed disruption of microtubules, resulting in ectopic arborization of dendrites, and axon degeneration. Interestingly, overexpression of TBCD also resulted in microtubule disruption and ectopic dendrite arborization, suggesting that an optimum level of TBCD is crucial for in vivo neuronal morphogenesis. We further found that TBCD physically interacts with the intracellular domain of Down syndrome cell adhesion molecule (Dscam), which is important for neural development and has been implicated in Down syndrome. Genetic analyses revealed that TBCD cooperates with Dscam in vivo. Our study may offer new insights into the molecular mechanism underlying the altered neural networks in cognitive disabilities of Down syndrome.

  10. The Hippo tumor suppressor pathway triggers non-cell autonomous tumorigenesis in Drosophila

    Daichi Honda, Misako Okumura, Ayano Oi, Chisako Sakuma, Fumiaki Obata, Toshinori Ando, Masayuki Miura, Takahiro Chihara

    EMBO Reports　2026/05/01

    DOI： 10.1038/s44319-026-00778-5 　

  11. Generation of Odorant Receptor-QF2 Knock-In Drivers for Improved Analysis of Olfactory Circuits in Drosophila Peer-reviewed

    Ukita, Yumiko, Suzuki, Ryoka, Miyoshi, Keita, Saito, Kuniaki, Okumura, Misako, Chihara, Takahiro

    GENES TO CELLS　30　(4)　2025/07

    Publisher: WILEY

    DOI： 10.1111/gtc.70028 　

    ISSN： 1356-9597

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    Drosophila melanogaster has provided numerous insights into the olfactory system, primarily relying on a series of transgenic Gal4 drivers. The combined use of Gal4/UAS and a second binary expression system, such as the QF/QUAS system, provides the opportunity to manipulate the two distinct cell populations, thereby accelerating the elucidation of the olfactory neural mechanisms. However, resources apart from the Gal4/UAS system have been poorly developed. In this study, we generated a series of odorant receptor (Or)-QF2 knock-in driver (Or-QF2KI) lines for 23 Ors using the CRISPR/Cas9 knock-in method. In these lines, the QF2 protein is cotranslated with each Or product. The expression pattern of the Or-QF2KI drivers mostly corresponded to that of the Or-Gal4 drivers. In addition, the Or42a-QF2KI driver identified the additional expression pattern of Or42a, which is consistent with the data of single-nucleus RNA sequencing and is attributed to the Or-QF2KI drivers' ability to reflect the endogenous expression of the Or genes. Thus, these Or-QF2KI drivers can be used as valuable genetic tools for olfactory research in Drosophila.

  12. Hippo-activated cells induce non-cell autonomous tumorigenesis in Drosophila

    Daichi Honda, Misako Okumura, Chisako Sakuma, Toshinori Ando, Masayuki Miura, Takahiro Chihara

    2025/05/06

    DOI： 10.1101/2025.05.05.652237 　

  13. Secretion of endoplasmic reticulum protein VAPB/ALS8 requires topological inversion

    Kosuke Kamemura, Rio Kozono, Mizuki Tando, Misako Okumura, Daisuke Koga, Satoshi Kusumi, Kanako Tamai, Aoi Okumura, Sayaka Sekine, Daichi Kamiyama, Takahiro Chihara

    Nature Communications　15　(1)　2024/10/10

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41467-024-53097-5 　

    eISSN： 2041-1723

  14. Executioner caspase is proximal to Fasciclin 3 which facilitates non-lethal activation in Drosophila olfactory receptor neurons

    Masaya Muramoto, Nozomi Hanawa, Misako Okumura, Takahiro Chihara, Masayuki Miura, Natsuki Shinoda

    eLife　2024/09/26

    Publisher: eLife Sciences Publications, Ltd

    DOI： 10.7554/elife.99650 　

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    The nervous system undergoes functional modification independent on cell turn over. Caspase participates in reversible neuronal modulation via non-lethal activation. However, the mechanism that enables non-lethal activation remains unclear. Here, we analyzed proximal proteins of Drosophila executioner caspase in the adult brain using TurboID. We discovered that executioner caspase Drice is, as an inactive proform, proximal to cell membrane proteins, including a specific splicing isoform of cell adhesion molecule Fasciclin 3 (Fas3), Fas3G. To investigate whether sequestration of executioner caspase to plasma membrane of axons is the mechanism for non-lethal activation, we developed a Gal4-Manipulated Area-Specific CaspaseTracker/CasExpress system for sensitive monitoring of caspase activity near plasma membrane. We demonstrated that Fas3G-overexpression promotes caspase activation in olfactory receptor neurons without killing them, by inducing expression of initiator caspase Dronc, which also comes close to Fas3G. Physiologically, Fas3G-overexpression facilitated non-lethal activation suppresses innate olfactory attraction behavior. Our findings suggest that subcellularly-restricted caspase activation, defined by caspase proximal proteins, is the mechanism for non-lethal activation, opening the methodological development of reversible modification of neuronal function via regulating caspase proximal proteins.

  15. Glutamate, GABA, and dense-core vesicle secretion regulate predatory feeding in the nematodePristionchus pacificus

    Ageha Onodera, Andrew Zhang, Takahiro Chihara, Ralf J. Sommer, Misako Okumura

    2024/06/22

    DOI： 10.1101/2024.06.18.599456 　

  16. Akaluc/AkaLumine bioluminescence system enables highly sensitive, non-invasive and temporal monitoring of gene expression in Drosophila Peer-reviewed

    Akira Ito, Nagisa Matsuda, Yumiko Ukita, Misako Okumura, Takahiro Chihara

    Communications Biology　2023/11

    DOI： 10.1038/s42003-023-05628-x 　

  17. Crosstalk between the mTOR and Hippo pathways Peer-reviewed

    Daichi Honda, Misako Okumura, Takahiro Chihara

    Development, Growth & Differentiation　65　(6)　337-347　2023/06/14

    Publisher: Wiley

    DOI： 10.1111/dgd.12867 　

    ISSN： 0012-1592

    eISSN： 1440-169X

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    Abstract Cell behavior changes in response to multiple stimuli, such as growth factors, nutrients, and cell density. The mechanistic target of the rapamycin (mTOR) pathway is activated by growth factors and nutrient stimuli to regulate cell growth and autophagy, whereas the Hippo pathway has negative effects on cell proliferation and tissue growth in response to cell density, DNA damage, and hormonal signals. These two signaling pathways must be precisely regulated and integrated for proper cell behavior. This integrative mechanism is not completely understood; nevertheless, recent studies have suggested that components of the mTOR and Hippo pathways interact with each other. Herein, as per contemporary knowledge, we review the molecular mechanisms of the interaction between the mTOR and Hippo pathways in mammals and Drosophila. Moreover, we discuss the advantage of this interaction in terms of tissue growth and nutrient consumption.

  18. Dynamin-2 regulates microtubule stability via an endocytosis-independent mechanism. International-journal

    Runzhao Guo, Ryuji Fujito, Akira Nagasaki, Misako Okumura, Takahiro Chihara, Kozue Hamao

    Cytoskeleton (Hoboken, N.J.)　2022/08/26

    DOI： 10.1002/cm.21723 　

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    Microtubule stability and dynamics regulations are essential for vital cellular processes, such as microtubule-dependent axonal transport. Dynamin is involved in many membrane fission events, such as clathrin-mediated endocytosis. The ubiquitously expressed dynamin-2 has been reported to regulate microtubule stability. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the roles of intrinsic properties of dynamin-2 on microtubule regulation by rescue experiments. A heterozygous DNM2 mutation in HeLa cells was generated, and an increase in the level of stabilized microtubules in these heterozygous cells was observed. The expression of wild-type dynamin-2 in heterozygous cells reduced stabilized microtubules. Conversely, the expression of self-assembly-defective mutants of dynamin-2 in the heterozygous cells failed to decrease stabilized microtubules. This indicated that the self-assembling ability of dynamin-2 is necessary for regulating microtubule stability. Moreover, the heterozygous cells expressing the GTPase-defective dynamin-2 mutant, K44A, reduced microtubule stabilization, similar to the cells expressing wild-type dynamin-2, suggesting that GTPase activity of dynamin-2 is not essential for regulating microtubule stability. These results showed that the mechanism of microtubule regulation by dynamin-2 is diverse from that of endocytosis. This article is protected by copyright. All rights reserved.

  19. Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila Peer-reviewed

    Ukita, Yumiko, Okumura, Misako, Chihara, Takahiro

    GENES TO CELLS　27　(6)　381-391　2022/06

    Publisher: WILEY

    DOI： 10.1111/gtc.12935 　

    ISSN： 1356-9597

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    Sleep is regulated by two main processes: the circadian clock and sleep homeostasis. Circadian rhythms have been well studied at the molecular level. In the Drosophila circadian clock neurons, the core clock proteins are precisely regulated by post-translational modifications and degraded via the ubiquitin-proteasome system (UPS). Sleep homeostasis, however, is less understood; nevertheless, recent reports suggest that proteasome-mediated degradation of core clock proteins or synaptic proteins contributes to the regulation of sleep amount. Here, we review the molecular mechanism of the UPS and summarize the role of protein degradation in the regulation of circadian clock and homeostatic sleep in Drosophila. Moreover, we discuss the potential interaction between circadian clock and homeostatic sleep regulation with a prime focus on E3 ubiquitin ligases.

  20. Endoplasmic reticulum proteins Meigo and Gp93 govern dendrite targeting by regulating Toll-6 localization Peer-reviewed

    Kamemura, Kosuke, Moriya, Hiroyuki, Ukita, Yumiko, Okumura, Misako, Miura, Masayuki, Chihara, Takahiro

    DEVELOPMENTAL BIOLOGY　484　30-39　2022/04

    Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE

    DOI： 10.1016/j.ydbio.2022.02.002 　

    ISSN： 0012-1606

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    Neuronal target recognition is performed by numerous cell-surface transmembrane proteins. Correct folding of these proteins occurs in the endoplasmic reticulum (ER) lumen of the neuronal cells before being transported to the plasma membrane of axons or dendrites. Disturbance in this protein folding process in the ER leads to dysfunction of neuronal cell surface molecules, resulting in abnormal neuronal targeting. In this study, we report that the ER-resident protein Meigo in Drosophila, governs the dendrite targeting of olfactory projection neurons (PNs) along the mediolateral axis of the antennal lobe by regulating Toll-6 localization. Loss of Meigo causes Toll 6 mislocalization in the PNs and mediolateral dendrite targeting defects, which are suppressed by Toll-6 over expression. Furthermore, we found that the ER-chaperone protein, Gp93, also regulates the mediolateral targeting of PN dendrites by localization of the Toll-6 protein. Gp93 overexpression in the PN homozygous for the meigo mutation, partially rescued the dendrite targeting defect, while meigo knockdown decreased Gp93 expression levels in cultured cells. These results indicate that the ER-proteins Meigo and Gp93 regulate dendrite targeting by attenuating the amount and localization of cell surface receptors, including Toll-6, implying the unexpected but active involvement of ER proteins in neural wiring.

  21. Systemic innate immune response induces death of olfactory receptor neurons in Drosophila Peer-reviewed

    Takeuchi, Ken-ichi, Honda, Daichi, Okumura, Misako, Miura, Masayuki, Chihara, Takahiro

    GENES TO CELLS　27　(2)　113-123　2022/02

    Publisher: WILEY

    DOI： 10.1111/gtc.12914 　

    ISSN： 1356-9597

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    Neural functions are known to decline during normal aging and neurodegenerative diseases. However, the mechanisms of functional impairment owing to the normal aging of the brain are poorly understood. Previously, we reported that caspase-3-like protease, the protease responsible for inducing apoptosis, is activated in a subset of olfactory receptor neurons (ORNs), especially in Drosophila Or42b neurons, during normal aging. Herein, we investigated the molecular mechanism underlying age-related caspase-3-like protease activation and cell death in Or42b neurons. Gene expression profiling of young and aged fly antenna showed that the expression of antimicrobial peptides was significantly upregulated, suggesting an activated innate immune response. Consistent with this observation, inhibition or activation of the innate immune pathway caused delayed or precocious cell death, respectively, in Or42b neurons. Accordingly, autonomous cell activation of the innate immune pathway in Or42b neurons is not likely required for their age-related death, whereas the systemic innate immune response induces caspase-3-like protease activation in Or42b neurons; this indicated that the death of these neurons is regulated non-cell autonomously. We propose a possible link between the innate immune response and the death of olfactory neurons during normal aging.

  22. Efficient visual screening of CRISPR/Cas9 genome editing in the nematode Pristionchus pacificus Invited Peer-reviewed

    Hiraga, Hirokuni, Ishita, Yuuki, Chihara, Takahiro, Okumura, Misako

    DEVELOPMENT GROWTH & DIFFERENTIATION　63　(9)　488-500　2021/12

    DOI： 10.1111/dgd.12761 　

    ISSN： 0012-1592

    eISSN： 1440-169X

  23. Spatial transcriptomics of nematodes identifies sperm cells as a source of genomic novelty and rapid evolution International-coauthorship Peer-reviewed

    Christian Rödelsperger, Annabel Ebbing, Devansh Raj Sharma, Misako Okumura, Ralf J Sommer, Hendrik C Korswagen

    Molecular Biology and Evolution　38　229-243　2021

    ISSN： 0737-4038

  24. Amyotrophic lateral sclerosis-associated VAP33 is required for maintaining neuronal dendrite morphology and organelle distribution in Drosophila Peer-reviewed

    Kosuke Kamemura, Chun‐an Chen, Misako Okumura, Masayuki Miura, Takahiro Chihara

    Genes to Cells　26　230-239　2021

    DOI： 10.1111/gtc.12835 　

    ISSN： 1356-9597

  25. Impairment of cytokinesis by cancer-associated DAPK3 mutations Peer-reviewed

    Ono, T., Terada, F., Okumura, M., Chihara, T., Hamao, K

    Biochemical and Biophysical Research Communications　533　(4)　1095-1101　2020/12/17

    ISSN： 0006-291X

  26. Serotonergic modulation of feeding behavior in Caenorhabditis elegans and other related nematodes. International-journal Peer-reviewed

    Yuuki Ishita, Takahiro Chihara, Misako Okumura

    Neuroscience research　154　9-19　2019/04/24

    DOI： 10.1016/j.neures.2019.04.006 　

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    Serotonin is a conserved neuromodulator that controls feeding behavior in response to environmental inputs in a wide range of species, including the nematode, Caenorhabditis elegans. To understand the detailed mechanism and evolution of serotonergic neuromodulation, the feeding behaviors of C. elegans and related species have been studied intensively because of their simple neural anatomy and genetic manipulability. C. elegans shows patterned movements of a feeding structure called the pharynx, and serotonin modulates feeding rhythms via several serotonin receptors expressed in pharyngeal motor neurons and muscles. Environmental inputs and physiological states like food signals, starvation, and heat affect the activity of serotonergic neurons and downstream neural pathways. We focus on serotonergic neural pathways in the feeding behavior of C. elegans and other nematodes, neuromodulation between environmental inputs and behavioral outputs, and their evolutionary path.

  27. Function of pioneer neurons specified by the basic helix-loop-helix transcription factor atonal in neural development. International-journal Invited Peer-reviewed

    Misako Okumura, Takahiro Chihara

    Neural regeneration research　11　(9)　1394-1395　2016/09

    DOI： 10.4103/1673-5374.191201 　

    ISSN： 1673-5374

  28. Assaying Predatory Feeding Behaviors in Pristionchus and Other Nematodes Peer-reviewed

    James W. Lightfoot, Martin Wilecki, Misako Okumura, Ralf J. Sommer

    JOVE-JOURNAL OF VISUALIZED EXPERIMENTS　(115)　e54404　2016/09

    DOI： 10.3791/54404 　

    ISSN： 1940-087X

  29. Hierarchical axon targeting of Drosophila olfactory receptor neurons specified by the proneural transcription factors Atonal and Amos. International-journal Peer-reviewed

    Misako Okumura, Tomoko Kato, Masayuki Miura, Takahiro Chihara

    Genes to cells : devoted to molecular & cellular mechanisms　21　(1)　53-64　2016/01

    DOI： 10.1111/gtc.12321 　

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    Sensory information is spatially represented in the brain to form a neural map. It has been suggested that axon-axon interactions are important for neural map formation; however, the underlying mechanisms are not fully understood. We used the Drosophila antennal lobe, the first olfactory center in the brain, as a model for studying neural map formation. Olfactory receptor neurons (ORNs) expressing the same odorant receptor target their axons to a single glomerulus out of approximately 50 glomeruli in the antennal lobe. Previous studies have showed that the axons of Atonal ORNs, specified by Atonal, a basic helix-loop-helix (bHLH) transcription factor, pioneer antennal lobe formation; however, the details remain to be elucidated. Here, we show that genetic ablation of Atonal ORNs affects antennal lobe structure and axon targeting of Amos ORNs, another type of ORN specified by the bHLH transcription factor Amos. During development, Atonal ORNs reach the antennal lobe and form the axon commissure before Amos ORNs. We also found that N-cadherin knockdown specifically in Atonal ORNs disrupts the glomerular boundary in the whole antennal lobe. Our results suggest that Atonal ORNs function as pioneer axons. Thus, correct axon targeting of Atonal ORNs is essential for formation of the whole antennal lobe.

  30. A STRIPAK component Strip regulates neuronal morphogenesis by affecting microtubule stability. International-journal Peer-reviewed

    Chisako Sakuma, Misako Okumura, Tomoki Umehara, Masayuki Miura, Takahiro Chihara

    Scientific reports　5　17769-17769　2015/12/08

    DOI： 10.1038/srep17769 　

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    During neural development, regulation of microtubule stability is essential for proper morphogenesis of neurons. Recently, the striatin-interacting phosphatase and kinase (STRIPAK) complex was revealed to be involved in diverse cellular processes. However, there is little evidence that STRIPAK components regulate microtubule dynamics, especially in vivo. Here, we show that one of the core STRIPAK components, Strip, is required for microtubule organization during neuronal morphogenesis. Knockdown of Strip causes a decrease in the level of acetylated α-tubulin in Drosophila S2 cells, suggesting that Strip influences the stability of microtubules. We also found that Strip physically and genetically interacts with tubulin folding cofactor D (TBCD), an essential regulator of α- and β-tubulin heterodimers. Furthermore, we demonstrate the genetic interaction between strip and Down syndrome cell adhesion molecule (Dscam), a cell surface molecule that is known to work with TBCD. Thus, we propose that Strip regulates neuronal morphogenesis by affecting microtubule stability.

  31. The roles of tubulin-folding cofactors in neuronal morphogenesis and disease. International-journal Invited Peer-reviewed

    Misako Okumura, Masayuki Miura, Takahiro Chihara

    Neural regeneration research　10　(9)　1388-9　2015/09

    DOI： 10.4103/1673-5374.165226 　

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Misc. 1

  1. Role of PCP protein Dachsous in the neural wiring of Drosophila olfactory system

    Misako Okumura, Masayuki Miura, Takahiro Chihara

    NEUROSCIENCE RESEARCH　71　E237-E237　2011

    DOI： 10.1016/j.neures.2011.07.1034 　

    ISSN： 0168-0102

Presentations 42

  1. Seeing without eyes: how nematodes respond to light Invited

    Hirokuni Hiraga, Ageha Onodera, Chinatsu Kai, Kenichi Nakayama, Keimei Ko, Takahiro Chihara, Misako Okumura

    RIKEN BDR Symposium 2026　2026/03/02

  2. Light-Induced Oxidative Stress and cGMP Signaling Regulate Mouth-Form Polyphenism in the nematode Pristionchus pacificus Invited

    Misako Okumura

    15th GfE School & GfE/JSDB young scientist workshop　2025/09/25

  3. Molecular Basis Underlying the Evolution of Feeding Behavior in Nematodes Invited

    Misako Okumura

    The 96th Annual Meeting of the Zoological Society of Japan　2025/09/04

  4. 目立ってなんぼ：“変わり者”たちと生命の謎に挑む Invited

    奥村美紗子

    令和7年度 広島大学女性科学技術フェローシップ制度 授与式・講演会　2025/07/24

  5. The molecular mechanisms of light adaptation in the nematode Pristionchus pacificus

    Aya Manabe, Keimei Ko, Kenichi Nakayama, Takahiro Chihara, and Misako Okumura

    25th International Worm Meeting　2025/06/28

  6. ゲノム編集で迫る“線虫を食べる線虫”の行動進化メカニズム Invited

    奥村美紗子

    広島大学卓越大学院プログラム先端科学セミナー“ゲノム編集”で未来社会を拓く　2024/12/05

  7. The eyeless nematode Pristionchus pacificus responds to light via the cGMP pathway and a GPCR kinase

    Kenichi Nakayama, Hirokuni Hiraga, Aya Manabe, Takahiro Chihara, Misako Okumura

    Neuro2024　2024/07/24

  8. Light avoidance mechanism through the cGMP pathway and GPCR kinase in Pristionchus pacificus

    Kenichi Nakayama, Hirokuni Hiraga, Aya Manabe, Takahiro Chihara, Misako Okumura

    C. elegans Topic Meeting: Neuronal Development, Synaptic Function & Behavior　2024/06/23

  9. The effect of light-induced oxidative stress on mouth form polyphenism in the nematode Pristionchus pacificus

    Hirokuni Hiraga, Ageha Onodera, Kenichi Nakayama, Chinatsu Kai, Takahiro Chihara, Misako Okumura

    Metabolism, Aging, Pathogenesis, Stress, and Small RNAs in C. elegans meeting　2024/06/20

  10. Light influences mouth form polyphenism through the cGMP pathway in the nematode Pristionchus pacificus Invited

    Misako Okumura

    12th Tokyo Tech International Symposium on Life Science and Technology, Photon explores new frontiers of biology, chemistry and medical therapy　2024/01/24

  11. Light and oxidative stress influence the mouth form dimorphism in the nematode Pristionchus pacificus Invited

    Misako Okumura

    The 46th Annual Meeting of the Molecular Biology Society of Japan　2023/12/08

  12. Establishment of genetic tools for analyzing neural functions in Pristionchus pacificus

    Misako Okumura

    4th International Pristionchus meeting　2023/09/22

  13. The co-option of a grinder-molting protease is essential for predatory feeding in the nematode Pristionchus pacificus

    Misako Okumura

    24th International C. elegans Conference　2023/06/26

  14. Regulation and evolutionary mechanisms of predatory behavior in the nematode Pristionchus pacificus Invited

    Misako Okumura

    2022/12/10

  15. Light exposure during development influences the mouth form dimorphism in the nematode Pristionchus pacificus

    Ageha Onodera, Hirokuni Hiraga, Yuuki Ishita, Ken-ichi Nakayama, Chinatsu Kai, Takahiro Chihara, Misako Okumura

    3rd Franco-Japanese Developmental Biology meeting　2022/11/07

  16. Molecular and neural mechanisms of light avoidance behavior in the nematode Pristionchus pacificus

    2022/10/05

  17. An astacin metalloprotease is required for predation in the nematode Pristionchus pacificus Invited

    Misako Okumura

    Asia-Pacific Worm Meeting 2022　2022/07/18

  18. The evolution of multiple traits associated with a derivative feeding habit is mediated by co-option of an astacin metalloprotease in the nematode Pristionchus pacificus

    Yuuki Ishita, Takahiro Chihara, Misako Okumura

    2022/05/31

  19. 線虫における光忌避行動の分子・神経基盤の解明

    中山賢一, 千原崇裕, 奥村美紗子

    第44回日本分子生物学会年会　2021/12/01

  20. Forward genetic screening to understand the molecular mechanism responding to light in P. pacificus

    Ken-ichi Nakayama, Ageha Onodera, Chinatsu Kai, Takahiro Chihara, Misako Okumura

    2nd International Pristionchus meeting　2021/10/13

  21. 光環境による表現型多型の制御機構 Invited

    奥村美紗子

    第6回HiHA Young Researchers Workshop 東広島統合生命科学・霞医系科学横断若手ワークショップ　2021/06/23

  22. Predatory feeding behavior is modulated via three serotonin receptors and other genetic factors in the nematode Pristionchus pacificus

    Yuuki Ishita, Takahiro Chihara, Misako Okumura

    23rd international C. elegans conference　2021/06/21

  23. Exposure of light affects the mouth form dimorphism in the nematode Pristionchus pacificus

    Chinatsu Kai, Takahiro Chihara, Misako Okumura

    2021/06/17

  24. CRISPR/Cas9 injection marker in the nematode Pristionchus pacificus

    Misako Okumura

    Future of the Nematodes Studies 2019　2019/08/21

  25. Screening for CRISPR/Cas9-induced mutations using microchip electrophoresis in the nematode Pristionchus pacificus International-presentation

    Misako Okumura

    22nd International C. elegans Conference　2019/06/20

  26. Neural mechanism of predatory feeding behavior in nematode Pristionchus pacificus

    Misako Okumura

    The 41st Annual Meeting of the Molecular Biology Society of Japan　2018/11/28

  27. Neuro Evo Devoモデルとしての線虫Pristionchus pacificusの魅力と展望

    Misako Okumura

    Future of the nematodes studies　2018/09/14

  28. Neural regulation of the predatory feeding behavior in Pristionchus pacificus International-presentation

    Misako Okumura, Yuuki Ishita, Ralf J Sommer, Takahiro Chihara

    8th Asia Pacific Worm Meeting　2018/07/09

  29. Function of Serotonin in Regulation of Predatory Feeding Behavior in the Nematode Pristionchus pacificus

    Misako Okumura, Martin Wilecki, Ralf Sommer

    2017/12/06

  30. Serotonin regulates predatory feeding behavior in nematode Pristionchus pacificus

    Misako Okumura, Martin Wilecki, Ralf J Sommer

    2017/09/21

  31. Serotonin is required for Efficient Predatory Feeding by Pristionchus pacificus Predators. International-presentation

    Misako Okumura

    C. elegans Topic Meeting: Neuronal development, Synaptic function and Behavior　2016/08/27

  32. Serotonin regulates dynamic feeding mode switching inducing predatory kinetics in Pristionchus pacificus. International-presentation

    Misako Okumura

    20th International C.elegans meeting　2015/06/24

  33. Tubulin folding cofactor D cooperates with Dscam during neuronal morphogenesis International-presentation

    Misako Okumura

    European Fly Neurobiology　2014/10/05

  34. Tubulin folding cofactor D regulates neuronal morphogenesis by mediating Dscam functions

    Misako Okumura

    Japanese Drosophila Research Conference 11　2014/06/04

  35. Linking cell surface receptor to microtubule: Tubulin folding cofactor D mediates Dscam functions during neuronal morphogenesis International-presentation

    Misako Okumura

    55th Annual Drosophila Research Conference　2014/03/26

  36. Role of tubulin folding pathway in neurite morphogenesis of Drosophila olfactory projection neuron

    Misako Okumura

    The 46th Annual Meeting for the Japanese Society of Developmental Biologists　2013/05/28

  37. Role of PCP signal molecule Four-jointed in dendrite morphogenesis of olfactory projection neuron.

    Misako Okumura

    Japanese Drosophila Research Conference 10　2012/10/13

  38. PCP signal molecule Four-jointed is involved in dendrite morphogenesis of olfactory projection neuron International-presentation

    Misako Okumura

    14th European Drosophila Neurobiology Meeting　2012/09/03

  39. Role of PCP signal molecule Four-jointed in dendrite targeting of Drosophila olfactory projection neuron

    Misako Okumura

    Joint Meeting of The 45th Annual Meeting for the Japanese Society of Developmental Biologists and The 64th Annual Meeting of the Japan Society for Cell Biology　2012/05/28

  40. Role of PCP protein Dachsous in the neural wiring of Drosophila olfactory system

    Misako Okumura

    The 34th Annual Meeting of the Japan Neuroscience Society　2011/09/14

  41. Role of a PCP protein Dachsous in Dendritic Targeting of Olfactory Projection Neurons International-presentation

    Misako Okumura

    1st Asia-Pacific Drosophila Research Conference　2011/05/22

  42. PCP protein Dachsous is required for dendritic targeting of olfactory projection neurons in Drosophila

    Misako Okumura

    The 44th Annual Meeting for the Japanese Society of Developmental Biologists　2011/05/18

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Research Projects 11

  1. 動物における第4の光受容体が拓く光生物学の新領域

    奥村 美紗子

    Offer Organization: 科学技術振興機構

    System: 戦略的な研究開発の推進 創発的研究支援事業

    Institution: 広島大学

    2023 - 2029

    More details Close

    光を受容し応答することは生存にとって重要であり、動物では大きく分けて3種類の光受容体が報告されています。線虫は目を持たず、既知の光受容体も持っていませんが、光に対して忌避行動を示します。そのため、線虫は動物における第4の光受容体を持つと考えられ、私はこの未知の光受容体の同定に挑戦します。さらに光による発生制御、光による線虫防除に焦点を当て、光受容体を軸とした光生物学の新たな研究領域の創出を目指します。

  2. 光環境依存的な表現型多型における組織間作用メカニズムの解明

    奥村 美紗子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 広島大学

    2025/04/01 - 2028/03/31

  3. 光環境に応じた表現型多型の分子・神経制御の解明

    奥村美紗子

    Offer Organization: 山田科学振興財団

    System: 山田科学振興財団 2023年度研究援助

    2023 - 2025

  4. 酸化ストレスに応答する表現型多型の制御機構

    Offer Organization: 三菱財団自然科学研究助成

    System: 若手助成

    2023/10 -

  5. 酸化ストレス依存的な表現型多型の制御メカニズムの解明

    Offer Organization: 公益信託成茂動物科学振興基金

    2023/10 -

  6. Molecular and neural mechanism of polyphenism responding to light Competitive

    Misako Okumura

    Offer Organization: Japan Agency for Medical Research and Development

    System: AMED-PRIME

    2019 - 2022

  7. Identification of novel photoreceptors in the nematode Pristionchus pacificus

    Misako Okumura

    Offer Organization: JSPS

    System: Grant-in-Aid for Young Scientists

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Hiroshima University

    2020 - 2021

    More details Close

    The nematode Pristionchus pacificus has no eyes and no known photoreceptors in its genome, but it can respond to light and exhibits light avoidance behavior. In this study, we aimed to clarify how the nematode P. pacificus senses light. We have established an assay system for light avoidance behavior and found that P. pacificus exhibits avoidance behavior in response to short-wavelength light. We conducted a forward genetic screening and isolated six mutant lines that did not show light-avoidance behavior, and identified the causal genes in five mutant lines. In addition, we identified candidate light-sensing cells and will confirm whether these cells are involved in light sensing, aiming to elucidate the molecular and neural mechanisms of light sensing.

  8. Neural mechanism of behavioral plasticity in nematode Pristionchus pacificus

    Okumura Misako

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Hiroshima University

    2018/04 - 2020/03

    More details Close

    Polyphenism is a phenomenon that organisms show distinct phenotypes depending on the surrounding environment. Animals exhibiting polyphenism often show behavioral plasticity but the neural mechanism of behavioral plasticity is largely unknown. To address this question, we focused on behavioral plasticity in feeding behaviors in nematode Pristionchus pacificus, which shows polyphenism in its mouth form. We generated mutants in neurotransmitter-related genes by CRISPR/Cas9 genome editing method and found that serotonin and subset of serotonin receptors are involved in feeding behaviors in P. pacificus.

  9. The molecular and neural mechanism of nematode light avoidance behavior Competitive

    Misako Okumura

    Offer Organization: Molecular Biology Society of Japan

    System: Tomizawa Jun-ichi & Keiko Fund of Molecular Biology Society of Japan for Young Scientist

    2019 - 2020

  10. 表現型可塑性に伴う行動多型の神経制御機構の解明 Competitive

    奥村美紗子

    Offer Organization: 広島大学教育研究支援財団

    System: 広島大学教育研究支援財団研究助成金

    2017 - 2018

  11. 脳内単一細胞モザイク解析法および光遺伝学による樹状突起ターゲティング機能の解明

    奥村 美紗子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 特別研究員奨励費

    Institution: 東京大学

    2012/04 - 2015/03

    More details Close

    機能的な神経回路網形成には、神経細胞の軸索と樹状突起が標的へ厳密に投射し、正しい結合相手と配線することが不可欠である。この過程において, 軸索と樹状突起は種々の細胞膜分子を介して周囲の情報を認識し、下流のシグナル経路に伝達することによって、 細胞骨格分子のリモデリングを行ない、正しい標的へと投射している。 しかしその分子機構は完全には解明されていない。本研究では神経形態形成の分子機構を明らかにするために、ショウジョウバエ嗅覚系投射神経をモデルに用いた。投射神経の樹状突起は触角葉に存在する約50個の糸球体のうち、単一の糸球体へと投射し、軸索は高次領域へと伸長し末端において特徴的な枝分かれをもっている。 遺伝学的手法を用いることによって、投射神経の形態を脳内において、単一細胞レベルで観察することが可能である。私は投射神経の形態形成に関わる分子を同定するために、候補となる遺伝子dachsousの変異体表現型解析を行った。そしてバックグラウンド変異としてチューブリン折りたたみ補因子D (Tubulin folding cofactor D (TBCD) )の変異を同定し、TBCDが投射神経の形態形成に必要であることを見出した。TBCDは5つのチューブリン折りたたみ補因子の一つであり、チューブリン二量体の形成に不可欠である。さらにTBCDと相互作用する分子として、ダウン症細胞接着分子(Dscam)を同定し、TBCDとDscamが遺伝的に相互作用することを見出した。TBCDの神経系での働きはこれまで知られておらず, この成果は国際学術雑誌Journal of Neuroscienceに掲載された。 <br> <br>

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Media Coverage 4

  1. 目のない線虫も光を感知している

    JST　JST news

    2025/02

    Type: Promotional material

  2. 広島大，線虫の光受容に関わる遺伝子や神経を発見

    Optronics　https://optronics-media.com/news/20241115/95814/

    2024/11/15

    Type: Internet

  3. 広島大、線虫Pristionchus pacificusの光忌避行動に関与する遺伝子および神経を発見

    日本経済新聞

    2024/11

    Type: Newspaper, magazine

  4. 広島大学の若手研究者に聞く，環境依存的な生物の形づくりと光感知を研究

    ザ・ウィークリー・プレスネット

    2023/12