Research activity information

• Aug. 2023 第２回山形大学異分野交流学会, 優秀賞


• Apr. 2022 令和3年度 山形大学研究推進報奨


• Mar. 2021 令和２年度 山形大学研究推進報奨


• Mar. 2020 令和元年度 山形大学研究推進報奨


• Mar. 2019 平成30年度 山形大学研究推進報奨


• Mar. 2018 平成29年度 山形大学研究推進報奨


• Sep. 2017 日本動物学会, 日本動物学会奨励賞


• Mar. 2015 平成26年度 山形大学研究推進報奨


• Mar. 2014 平成25年度 山形大学研究推進報奨


• May 2012 第45回日本発生生物学会 第64回日本細胞生物学会 合同大会, 若手優秀ポスター賞

• A novel mouse model of adenine-supplemented high-fat diet induced cardiovascular-kidney-metabolic syndrome

  Hiroe Ono, Yoichiro Otaki, Tetsu Watanabe, Ryuhei Yamaguchi, Tomohiro Takehara, Shingo Tachibana, Jun Goto, Takanori Arimoto, Haruki Ochi, Masafumi Watanabe

  Abstract Cardiovascular-kidney-metabolic (CKM) syndrome, a recently proposed concept focusing on the interrelationship among cardiovascular system, chronic kidney disease, and metabolic risk factors, is associated with high morbidity and mortality. The mechanism of CKM syndrome has not yet been fully examined due to the lack of an animal model. Here, we investigated whether an adenine-supplemented high-fat diet (AHFD) can induce CKM syndrome in mice. We fed normal chow diet (NCD), adenine-supplemented diet (AD), high-fat diet (HFD), and 0.15% AHFD to 129×1/Sv mice for 16 weeks and 0.2%AHFD to 129×1/Sv for 6 weeks. Also, C57BL/6 N mice were fed with 0.15%AHFD for 16 weeks. Metabolic parameters, blood pressure, organ weights, histology, and RNA sequencing were analyzed. The 0.15%AHFD group exhibited hypercholesterolemia, elevated blood pressure, kidney atrophy with fibrosis, and cardiac hypertrophy with interstitial fibrosis. Both kidney and cardiac RNA sequencing in the 0.15%AHFD group revealed upregulation of inflammatory and immune-related gene sets, whereas genes involved in cardiac contraction were downregulated. In contrast, 0.2%AHFD induced body weight loss, severe kidney dysfunction, and cardiac atrophy without functional impairment in 129×1/Sv mice. Of note, the C57BL/6 N mice exhibited metabolic abnormality and cardiac hypertrophy with diastolic dysfunction after 0.15%AHFD feeding despite mild renal dysfunction. We report a novel mouse model of CKM syndrome with dietary intervention, which exhibits fibrosis and myocardial hypertrophy in the heart. This model could be a valuable tool for analyzing the mechanism of CKM syndrome and assessing therapeutic options.

  Springer Science and Business Media LLC, Apr. 2026, Hypertension Research

  [Refereed]

  Scientific journal


• Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration

  Georgios Tsissios, Marion Leleu, Kelly Hu, Alp Eren Demirtas, Hanrong Hu, Sabrina Vinzens, Toru Kawanishi, Evangelia Skoufa, Atharva Valanju, Alessandro Valente, Lorenzo Noseda, Haruki Ochi, Antonio Herrera, Selman Sakar, Mikiko Tanaka, Sara A. Wickström, Fides Zenk, Can Aztekin

  Why mammals cannot regenerate limbs like amphibians do presents a long-standing puzzle in biology. To uncover the underlying differences, we compared amputation responses of embryonic mouse ( Mus musculus ) and Xenopus laevis tadpole limbs. Lowering environmental oxygen or stabilizing the oxygen-sensitive hypoxia-inducible factor 1A (HIF1A) induced rapid wound healing in mouse limbs. This response was accompanied by altered cellular mechanics, metabolism, and a histone landscape that primed regenerative cell states. Conversely, Xenopus tadpole limbs retained these features even under high oxygen levels. Their reduced oxygen-sensing capacity was associated with decreased HIF1A-regulating gene expression. Our results thus identify species-specific oxygen-sensing capacity as a fundamental, targetable mechanism that can unlock latent regenerative programs in mammals.

  American Association for the Advancement of Science (AAAS), Apr. 2026, Science, 392(6794) (6794)

  [Refereed]

  Scientific journal


• The Regenerative Stage‐Defined Neurogenic Properties in the Spinal Cord of Xenopus laevis: Correlation Between Neurogenic Potential and Functional Repair of the Spinal Cord

  Ryohei Seki‐Omura, Yousuke Nakano, Shinichi Hayashi, Hikaru Iwashita, Hitoshi Yokoyama, Taro Koike, Yuki Sato, Souichi Oe, Yukie Hirahara, Haruki Ochi, Hajime Ogino, Koji Tamura, Mari Dezawa, Masaaki Kitada

  Feb. 2026, Journal of Comparative Neurology

  [Refereed]

  Scientific journal


• A comprehensive review of peroxiredoxin 4, a redox protein evolved in oxidative protein folding coupled with hydrogen peroxide detoxification

  Junichi Fujii, Haruki Ochi, Sohsuke Yamada

  Elsevier BV, Feb. 2025, Free Radical Biology and Medicine, 227, 336 - 354

  [Refereed]

  Scientific journal


• Diacylglycerol Kinase ζ Attenuates Doxorubicin‐Induced Cardiotoxicity Through p53 Degradation

  Shingo Tachibana, Yoichiro Otaki, Tetsu Watanabe, Jun Goto, Haruki Ochi, Toshiaki Tanaka, Hiroe Ono, Ryuhei Yamaguchi, Junya Sato, Hiroki Takahashi, Takanori Arimoto, Kaoru Goto, Masafumi Watanabe

  Jan. 2025, Journal of the American Heart Association, 14(1):e035608, English

  [Refereed]

  Scientific journal


• hoxc12/c13 as key regulators for rebooting the developmental program in Xenopus limb regeneration

  Aiko Kawasumi-Kita, Sang-Woo Lee, Daisuke Ohtsuka, Kaori Niimi, Yoshifumi Asakura, Keiichi Kitajima, Yuto Sakane, Koji Tamura, Haruki Ochi, Ken-ichi T. Suzuki, Yoshihiro Morishita

  Apr. 2024, Nature Communications, 15(1):3340

  [Refereed]


• Development of a heat-stable alkaline phosphatase reporter system for cis-regulatory analysis and its application to three-dimensional digital imaging of Xenopus embryonic tissues

  Sakagamia K, Igawa T, Saikawaa K, Sakaguchib Y, Hossain N, Kato C, Kinemori K, Suzuki N, Suzuki M, Kawaguchi A, Ochi H, Yuki Tajika Y, Ogino H

  2024, Development Growth and Differentiation

  [Refereed]


• Identification of tumor-related genes via RNA sequencing of tumor tissues in Xenopus tropicalis

  Kazuki Kitamura, Takayoshi Yamamoto, Haruki Ochi, Makoto Suzuki, Nanoka Suzuki, Takeshi Igawa, Tadashi Yoshida, Mitsuru Futakuchi, Hajime Ogino, Tatsuo Michiue

  Abstract Cancer treatment is still challenging because the disease is often caused by multiple mutations. Although genomic studies have identified many oncogenes and tumor suppressor genes, gene sets involved in tumorigenesis remain poorly understood. Xenopus, a genus of aquatic frogs, is a useful model to identify gene sets because it can be genetically and experimentally analyzed. Here, we analyzed gene expression in tumor tissues of three individuals in Xenopus tropicalis and identified 55 differentially expressed genes (DEGs). Gene ontology (GO) analysis showed that the upregulated genes in the tumor tissues were enriched in GO terms related to the extracellular matrix and collagen fibril organization. Hierarchical clustering showed that the gene expression patterns of tumor tissues in X. tropicalis were comparable to those of human connective, soft, and subcutaneous tissue-derived cancers. Additionally, pathway analysis revealed that these DEGs were associated with multiple pathways, including the extracellular matrix, collagen fibril organization, MET signaling, and keratan sulfate. We also found that the expression tendency of some DEGs that have not been well analyzed in the cancer field clearly determines the prognosis of human cancer patients. This study provides a remarkable reference for future experimental work on X. tropicalis to identify gene sets involved in human cancer.

  Springer Science and Business Media LLC, Aug. 2023, Scientific Reports, 13(1) (1)

  [Refereed]

  Scientific journal


• The shh limb enhancer is activated in patterned limb regeneration but not in hypomorphic limb regeneration in Xenopus laevis.

  Reimi Tada, Takuya Higashidate, Takanori Amano, Shoma Ishikawa, Chifuyu Yokoyama, Suzu Kobari, Saki Nara, Koshiro Ishida, Akane Kawaguchi, Haruki Ochi, Hajime Ogino, Nayuta Yakushiji-Kaminatsui, Joe Sakamoto, Yasuhiro Kamei, Koji Tamura, Hitoshi Yokoyama

  Xenopus young tadpoles regenerate a limb with the anteroposterior (AP) pattern, but metamorphosed froglets regenerate a hypomorphic limb after amputation. The key gene for AP patterning, shh, is expressed in a regenerating limb of the tadpole but not in that of the froglet. Genomic DNA in the shh limb-specific enhancer, MFCS1 (ZRS), is hypermethylated in froglets but hypomethylated in tadpoles: shh expression may be controlled by epigenetic regulation of MFCS1. Is MFCS1 specifically activated for regenerating the AP-patterned limb? We generated transgenic Xenopus laevis lines that visualize the MFCS1 enhancer activity with a GFP reporter. The transgenic tadpoles showed GFP expression in hoxd13-and shh-expressing domains of developing and regenerating limbs, whereas the froglets showed no GFP expression in the regenerating limbs despite having hoxd13 expression. Genome sequence analysis and co-transfection assays using cultured cells revealed that Hoxd13 can activate Xenopus MFCS1. These results suggest that MFCS1 activation correlates with regeneration of AP-patterned limbs and that re-activation of epigenetically inactivated MFCS1 would be crucial to confer the ability to non-regenerative animals for regenerating a properly patterned limb.

  May 2023, Developmental biology, English, International magazine

  [Refereed]

  Scientific journal


• Splashed E-box and AP-1 motifs cooperatively drive regeneration response and shape regeneration abilities

  Teruhisa Tamaki, Takafumi Yoshida, Eri Shibata, Hidenori Nishihara, Haruki Ochi, Atsushi Kawakami

  ABSTRACT Injury triggers a genetic program that induces gene expression for regeneration. Recent studies have identified regeneration-response enhancers (RREs); however, it remains unclear whether a common mechanism operates in these RREs. We identified three RREs from the zebrafish fn1b promoter by searching for conserved sequences within the surrounding genomic regions of regeneration-induced genes and performed a transgenic assay for regeneration response. Two regions contained in the transposons displayed RRE activity when combined with the −0.7 kb fn1b promoter. Another non-transposon element functioned as a stand-alone enhancer in combination with a minimum promoter. By searching for transcription factor-binding motifs and validation by transgenic assays, we revealed that the cooperation of E-box and activator protein 1 motifs is necessary and sufficient for regenerative response. Such RREs respond to variety of tissue injuries, including those in the zebrafish heart and Xenopus limb buds. Our findings suggest that the fidelity of regeneration response is ensured by the two signals evoked by tissue injuries. It is speculated that a large pool of potential enhancers in the genome has helped shape the regenerative capacities during evolution.

  The Company of Biologists, Feb. 2023, Biology Open, 12(2) (2), English, International magazine

  [Refereed]

  Scientific journal


• Air-breathing behavior underlies the cell death in limbs of Rana pirica tadpoles.

  Ono SF, Ingrid Rosenburg Cordeiro, Kishida O, Haruki Ochi, Mikiko Tanaka

  Abstract Amphibians shape their limbs by differential outgrowth of digits and interdigital regions. In contrast, amniotes employ cell death, an additional developmental system, to determine the final shape of limbs. Previous work has shown that high oxygen availability is correlated with the induction of cell death in developing limbs. Given the diversity of life histories of amphibians, it is conceivable that some amphibians are exposed to a high–oxygen environment during the tadpole phase and exhibit cell death in their limbs. Here, we examined whether air–breathing behavior underlies the cell death in limbs of aquatic tadpoles of the frog species Rana pirica. Our experimental approach revealed that R. pirica tadpoles exhibit cell death in their limbs that is likely to be induced by oxidative stress associated with their frequent air–breathing behavior.

  Springer Science and Business Media LLC, Jan. 2023, Zoological letters, 9(1) (1)

  [Refereed]

  Scientific journal


• Retinoic acid control of pax8 during renal specification of Xenopus pronephros involves hox and meis3

  Haruki Ochi

  2023, Developmental Biology

  [Refereed]

  Scientific journal


• Air-breathing behavior underlies the cell death in limbs of R. pirica tadpoles

  Ono F, Cordeiro IR, Kishida O, Ochi H, Tanaka M

  Dec. 2022, Zoological Letters

  [Refereed]


• Adrenergic receptor signaling induced by Klf15, a regulator of regeneration enhancer, promotes kidney reconstruction

  Nanoka Suzuki, Akinori Kanai, Yutaka Suzuki, Hajime Ogino, Haruki Ochi

  Aug. 2022, Proceedings of the National Academy of Sciences

  [Refereed]

  Scientific journal


• Optimization of CRISPR /Cas9‐mediated gene disruption in Xenopus laevis using a phenotypic image analysis technique

  Mikio Tanouchi, Takeshi Igawa, Nanoka Suzuki, Makoto Suzuki, Nusrat Hossain, Haruki Ochi, Hajime Ogino

  Wiley, Mar. 2022, Development, Growth & Differentiation

  Scientific journal


• Spontaneous neoplasia in the western clawed frog Xenopus tropicalis

  Makoto Suzuki, Takeshi Igawa, Nanoka Suzuki, Hajime Ogino and Haruki Ochi

  Corresponding, Aug. 2020, microPublication Biology

  [Refereed]


• Regeneration enhancers: A clue to reactivation of developmental genes

  Nanoka Suzuki, Haruki Ochi

  Jun. 2020, Development, Growth & Differentiation, 62(5) (5), 343 - 354

  [Refereed][Invited]

  Scientific journal


• Comparative analysis demonstrates cell type-specific conservation of SOX9 targets between mouse and chicken

  Satoshi Yamashita, Kensuke Kataoka, Hiroto Yamamoto, Tomoko Kato, Satoshi Hara, Katsushi Yamaguchi, Claire Renard-Guillet, Yuki Katou, Katsuhiko Shirahige, Haruki Ochi, Hajime Ogino, Tokujiro Uchida, Masafumi Inui, Shuji Takada, Shuji Shigenobu, Hiroshi Asahara

  Abstract SRY (sex-determining region Y)-box 9 (SOX9) is a transcription factor regulating both chondrogenesis and sex determination. Among vertebrates, SOX9’s functions in chondrogenesis are well conserved, while they vary in sex determination. To investigate the conservation of SOX9’s regulatory functions in chondrogenesis and gonad development among species, we performed chromatin immunoprecipitation sequencing (ChIP-seq) using developing limb buds and male gonads from embryos of two vertebrates, mouse and chicken. In both mouse and chicken, SOX9 bound to intronic and distal regions of genes more frequently in limb buds than in male gonads, while SOX9 bound to the proximal upstream regions of genes more frequently in male gonads than in limb buds. In both species, SOX palindromic repeats were identified more frequently in SOX9 binding regions in limb bud genes compared with those in male gonad genes. The conservation of SOX9 binding regions was significantly higher in limb bud genes. In addition, we combined RNA expression analysis (RNA sequencing) with the ChIP-seq results at the same stage in developing chondrocytes and Sertoli cells and determined SOX9 target genes in these cells of the two species and disclosed that SOX9 targets showed high similarity of targets in chondrocytes, but not in Sertoli cells.

  Springer Science and Business Media LLC, Aug. 2019, Scientific Reports, 9(1) (1)

  [Refereed]

  Scientific journal


• Environmental Oxygen Exposure Allows for the Evolution of Interdigital Cell Death in Limb Patterning

  Ingrid Rosenburg Cordeiro, Kaori Kabashima, Haruki Ochi, Keijiro Munakata, Chika Nishimori, Mara Laslo, James Hanken, Mikiko Tanaka

  Elsevier BV, Jul. 2019, Developmental Cell, 50(2) (2), 155 - 166.e4

  [Refereed]

  Scientific journal


• Xenopus Resources: Transgenic, Inbred and Mutant Animals, Training Opportunities, and Web-Based Support

  Marko Horb, Marcin Wlizla, Anita Abu-Daya, Sean McNamara, Dominika Gajdasik, Takeshi Igawa, Atsushi Suzuki, Hajime Ogino, Anna Noble

  Frontiers Media SA, Apr. 2019, Frontiers in Physiology, 10

  Scientific journal


• Arid3a regulates nephric tubule regeneration via evolutionarily conserved regeneration signal-response enhancers

  Nanoka Suzuki, Kodai Hirano, Hajime Ogino, Haruki Ochi

  Jan. 2019, eLife, English

  [Refereed]

  Scientific journal


• Reactivation of larval keratin gene (krt62.L) in blastema epithelium during Xenopus froglet limb regeneration

  Akira Satoh, Kazumasa Mitogawa, Nanami Saito, Miyuki Suzuki, Ken-ichi T. Suzuki, Haruki Ochi, Aki Makanae

  Dec. 2017, DEVELOPMENTAL BIOLOGY, 432(2) (2), 265 - 272, English

  [Refereed]

  Scientific journal


• Co-accumulation of cis-regulatory and coding mutations during the pseudogenization of the Xenopus laevis homoeologs six6.L and six6.S

  Haruki Ochi, Akane Kawaguchi, Mikio Tanouchi, Nanoka Suzuki, Tatsuki Kumada, Yui Iwata, Hajime Ogino

  Lead, Jul. 2017, DEVELOPMENTAL BIOLOGY, 427(1) (1), 84 - 92, English

  [Refereed]

  Scientific journal


• Genes coding for cyclin-dependent kinase inhibitors are fragile in Xenopus

  Toshiaki Tanaka, Haruki Ochi, Shuji Takahashi, Naoto Ueno, Masanori Taira

  Jun. 2017, DEVELOPMENTAL BIOLOGY, 426(2) (2), 291 - 300, English

  [Refereed]

  Scientific journal


• Conservatism and variability of gene expression profiles among homeologous transcription factors in Xenopus laevis

  Minoru Watanabe, Yuuri Yasuoka, Shuuji Mawaribuchi, Aya Kuretani, Michihiko Ito, Mariko Kondo, Haruki Ochi, Hajime Ogino, Akimasa Fukui, Masanori Taira, Tsutomu Kinoshita

  Jun. 2017, DEVELOPMENTAL BIOLOGY, 426(2) (2), 301 - 324, English

  [Refereed]

  Scientific journal


• Asymmetrically reduced expression of handl homeologs involving a single nucleotide substitution in a cis-regulatory element

  Haruki Ochi, Nanoka Suzuki, Akane Kawaguchi, Hajime Ogino

  May 2017, DEVELOPMENTAL BIOLOGY, 425(2) (2), 152 - 160, English

  [Refereed]

  Scientific journal


• Genome evolution in the allotetraploid frog Xenopus laevis

  Adam M. Session, Yoshinobu Uno, Taejoon Kwon, Jarrod A. C. Hapman, Atsushi Toyoda, Shuji Takahashi, Akimasa Fukui, Akira Hikosaka, Atsushi Suzuki, Mariko Kondo, Simon J. van Heeringen, Ian Quigley, Sven Heinz, Hajime Ogino, Haruki Ochi, Uffe Hellsten, Jessica B. . Lyons, Oleg Simakov, Nicholas Putnam, Jonathan Stites, Yoko Kuroki, Toshiaki Tanaka, Tatsuo Michiue, Minoru Watanabe, Ozren B. Ogdanovic, Ryan Lister, Georgios Georgiou, Sarita S. Paranjpe, Ila Van Kruijsbergen, Shengquiang Shu, Joseph Carlson, Tsutomu Kinoshita, Yuko Ohta, Shuuji Mawaribuchi, Jerry Jenkins, Jane Grimwood, Jeremy Schmutz, Therese Mitros, Sahar V. Mozaffari, Yutaka Suzuki, Yoshikazu Haramoto, Takamasa S. Yamamoto, Chiyo Takagi, Rebecca Heald, Kelly Miller, Christian Haudenschild, Jacob Kitzman, Takuya Nakayama, Yumi I. Zutsu, Jacques Robert, Joshua Fortriede, Kevin Burns, Vaneet Lotay, Kamran Karimi, Yuuri Yasuoka, Darwin S. Dichmann, Martin F. Flajnik, Douglas W. Houston, Jay Shendure, Louis DuPasquier, Peter D. Vize, Aaron M. Zorn, Michihiko Ito, Edward M. Marcotte, John B. . Wallingford, Yuzuru Ito, Makoto Asashima, Naoto Ueno, Yoichi Matsuda, Gert Jan C. . Veenstra, Asao Fujiyama, Richard M. Harland, Masanori Taira, Daniel S. Rokhsar

  Oct. 2016, Nature, 538(7625) (7625), 336 - +, English

  [Refereed]

  Scientific journal


• A Novel Cysteine Knot Protein for Enhancing Sperm Motility That Might Facilitate the Evolution of Internal Fertilization in Amphibians

  Misato Yokoe, Eriko Takayama-Watanabe, Yoko Saito, Megumi Kutsuzawa, Kosuke Fujita, Haruki Ochi, Yuni Nakauchi, Akihiko Watanabe

  Aug. 2016, PLOS ONE, 11(8) (8), e0160445, English

  [Refereed]

  Scientific journal


• Identification of distal enhancers for Six2 expression in pronephros

  Nanoka Suzuki, Kodai Hirano, Hajime Ogino, Haruki Ochi

  2015, INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 59(4-6) (4-6), 241 - 246, English

  [Refereed]

  Scientific journal


• Transcriptional regulators in the Hippo signaling pathway control organ growth in Xenopus tadpole tail regeneration

  Shinichi Hayashi, Haruki Ochi, Hajime Ogino, Aiko Kawasumi, Yasuhiro Kamei, Koji Tamura, Hitoshi Yokoyama

  Dec. 2014, DEVELOPMENTAL BIOLOGY, 396(1) (1), 31 - 41, English

  [Refereed]

  Scientific journal


• Six1 is a key regulator of the developmental and evolutionary architecture of sensory neurons in craniates

  Hiroshi Yajima, Makoto Suzuki, Haruki Ochi, Keiko Ikeda, Shigeru Sato, Ken-ichi Yamamura, Hajime Ogino, Naoto Ueno, Kiyoshi Kawakami

  May 2014, BMC BIOLOGY, 12, 40, English

  [Refereed]

  Scientific journal


• Differential use of paralogous genes via evolution of cis-regulatory elements for divergent expression specificities

  Haruki Ochi, Akane Kawaguchi, Hajime Ogino

  Springer Japan, Nov. 2013, New Principles in Developmental Processes, 279 - 289, English

  [Invited]

  In book


• Evolution of a tissue-specific silencer underlies divergence in the expression of pax2 and pax8 paralogues

  Haruki Ochi, Tomoko Tamai, Hiroki Nagano, Akane Kawaguchi, Norihiro Sudou, Hajime Ogino

  Lead, May 2012, Nature Communications, 3, 848, English

  [Refereed]

  Scientific journal


• Transcription factors involved in lens development from the preplacodal ectoderm

  Hajime Ogino, Haruki Ochi, Hasan Mahmud Reza, Kunio Yasuda

  Academic Press Inc., Mar. 2012, Developmental Biology, 363(2) (2), 333 - 347, English

  [Refereed]

  Scientific journal


• Transcription factors involved in lens development from the preplacodal ectoderm

  Hajime Ogino, Haruki Ochi, Hasan Mahmud Reza, Kunio Yasuda

  Mar. 2012, DEVELOPMENTAL BIOLOGY, 363(2) (2), 333 - 347, English

  [Refereed]


• Comparative expression analysis of the H3K27 demethylases, JMJD3 and UTX, with the H3K27 methylase, EZH2, in Xenopus

  Akane Kawaguchi, Haruki Ochi, Norihiro Sudou, Hajime Ogino

  2012, INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 56(4) (4), 295 - 300, English

  [Refereed]

  Scientific journal


• Comparative genomics-based identification and analysis of cis-regulatory elements

  Hajime Ogino, Haruki Ochi, Chihiro Uchiyama, Sarah Louie, Robert M. Grainger

  2012, Methods in Molecular Biology, 917, 245 - 263, English

  [Refereed]

  Scientific journal


• Photoporation of Biomolecules into Single Cells in Living Vertebrate Embryos Induced by a Femtosecond Laser Amplifier

  Yoichiroh Hosokawa, Haruki Ochi, Takanori Iino, Akihiro Hiraoka, Mikiko Tanaka

  Nov. 2011, PLOS ONE, 6(11) (11), e27677, English

  [Refereed]

  Scientific journal


• Different Requirement for Wnt/beta-Catenin Signaling in Limb Regeneration of Larval and Adult Xenopus

  Hitoshi Yokoyama, Tamae Maruoka, Haruki Ochi, Akio Aruga, Shiro Ohgo, Hajime Ogino, Koji Tamura

  Jul. 2011, PLOS ONE, 6(7) (7), e21721, English

  [Refereed]

  Scientific journal


• Conservation and diversification of cis-regulatory mechanisms of the pax2/5/8 paralog group in chordates

  Haruki Ochi

  2011, Molecular Biology of the Cell

  Scientific journal


• Conserved expression of mouse Six1 in the pre-placodal region (PPR) and identification of an enhancer for the rostral PPR

  Shigeru Sato, Keiko Ikeda, Go Shioi, Haruki Ochi, Hajime Ogino, Hiroshi Yajima, Kiyoshi Kawakami

  Aug. 2010, DEVELOPMENTAL BIOLOGY, 344(1) (1), 158 - 171, English

  [Refereed]

  Scientific journal


• Resources and transgenesis techniques for functional genomics in Xenopus

  Hajime Ogino, Haruki Ochi

  May 2009, DEVELOPMENT GROWTH & DIFFERENTIATION, 51(4) (4), 387 - 401, English

  [Refereed]


• Heterochronic Shift in Hox-Mediated Activation of Sonic hedgehog Leads to Morphological Changes during Fin Development

  Koji Sakamoto, Koh Onimaru, Keijiro Munakata, Natsuno Suda, Mika Tamura, Haruki Ochi, Mikiko Tanaka

  Apr. 2009, PLOS ONE, 4(4) (4), e5121, English

  [Refereed]

  Scientific journal


• Lbx2 regulates formation of myofibrils

  Haruki Ochi, Monte Westerfield

  Lead, Feb. 2009, BMC DEVELOPMENTAL BIOLOGY, 9, 13, English

  [Refereed]

  Scientific journal


• Resources and transgenesis techniques for functional genomics in Xenopus.

  Ogino Hajime, Ochi Haruki

  2009, Development, growth & differentiation, 51(4) (4)

  Scientific journal


• Smarcd3 regulates the timing of zebrafish myogenesis onset

  Haruki Ochi, Stefan Hans, Monte Westerfield

  Lead, Feb. 2008, JOURNAL OF BIOLOGICAL CHEMISTRY, 283(6) (6), 3529 - 3536, English

  [Refereed]

  Scientific journal


• Signaling networks that regulate muscle development: Lessons from zebrafish

  Haruki Ochi, Monte Westerfield

  Lead, Jan. 2007, DEVELOPMENT GROWTH & DIFFERENTIATION, 49(1) (1), 1 - 11, English

  [Refereed]


• Hhip regulates zebrafish muscle development by both sequestering Hedgehog and modulating localization of Smoothened

  Haruki Ochi, Bret J. Pearson, Pao-Tien Chuang, Matthias Hammerschmidt, Monte Westerfield

  Lead, Sep. 2006, DEVELOPMENTAL BIOLOGY, 297(1) (1), 127 - 140, English

  [Refereed]

  Scientific journal


• Temporal expression of L-Maf and RaxL in developing chicken retina are arranged into mosaic pattern

  H Ochi, K Sakagami, A Ishii, N Morita, M Nishiuchi, H Ogino, K Yasuda

  Sep. 2004, GENE EXPRESSION PATTERNS, 4(5) (5), 489 - 494, English

  [Refereed]

  Scientific journal


• The stability of the lens-specific maf protein is regulated by fibroblast growth factor (FGF)/ERK signaling in lens fiber differentiation

  H Ochi, H Ogino, Y Kageyama, K Yasuda

  Lead, Jan. 2003, JOURNAL OF BIOLOGICAL CHEMISTRY, 278(1) (1), 537 - 544, English

  [Refereed]

  Scientific journal

• Versatile utilities of amphibians (part 5)

  Haruki Ochi, Takashi Kato, Aaron Zorn, Toshinori Hayashi, Takeshi Inoue, Mariko Kondo, Masanori Taira, Tatsuo Michiue

  Lead, Wiley, 25 Oct. 2023, Development, Growth & Differentiation, 65(8) (8), 459 - 460


• Versatile utilities of amphibians (part 4)

  Haruki Ochi

  Lead, Jan. 2023, Development, Growth & Differentiation, 65(1) (1), 4 - 5


• Versatile utilities of amphibians (Part 3)

  Tatsuo Michiue, Takashi Kato, Haruki Ochi, Aaron Zorn, Toshinori Hayashi, Takeshi Inoue, Mariko Kondo, Masanori Taira

  Wiley, Dec. 2022, Development, Growth & Differentiation, 64(9) (9), 472 - 473


• Versatile utilities of amphibians (part 2)

  Tatsuo Michiue, Aaron M Zorn, Takashi Kato, Haruki Ochi, Toshinori Hayashi, Takeshi Inoue

  Wiley, Sep. 2022, Development, Growth & Differentiation, 64(7) (7), 346 - 346


• Versatile Utilities of Amphibians (part 1)

  Tatsuo Michiue, Aaron M. Zorn, Takashi Kato, Haruki Ochi, Toshinori Hayashi, Takeshi Inoue

  Wiley, Aug. 2022, Development, Growth & Differentiation, 64(6) (6), 264 - 265


• ゲノム倍加後のコード配列進化におけるエンハンサー減衰変異の促進的役割

  荻野肇, 越智陽城, 川口茜

  2016, 日本分子生物学会年会プログラム・要旨集(Web), 39th


• ヒストン脱メチル化因子Jmjd3による眼形成遺伝子pax6の発現制御

  川口茜, 越智陽城, 須藤則広, 荻野肇

  2015, 日本遺伝学会大会プログラム・予稿集, 87th


• Gene expression dynamics in the artificially genome duplicated vertebrate embryo

  Haruki Ochi

  Dec. 2014, GENES & GENETIC SYSTEMS, 89(6) (6), 282 - 282, English

  Summary international conference


• 発現調節配列の変化を探る - 多様性をつくる鍵はゲノムのどこにある？.

  越智 陽城

  Lead, 2014, 中村桂子(編) 変わる, 189 - 196


• ヒストンH3K27脱メチル化因子による細胞分化コンピテンスの制御

  荻野肇, 須藤則広, 川口茜, 越智陽城

  2014, 日本動物学会大会予稿集, 85th


• ヒストン脱メチル化因子Jmjd3による眼形成遺伝子Pax6の発現制御

  川口茜, 越智陽城, 須藤則広, 荻野肇

  2014, 日本遺伝学会大会プログラム・予稿集, 86th


• ツメガエル幼生の尾部再生時におけるヒストンメチル化制御因子の働き

  川口茜, 川口茜, 越智陽城, 須藤則広, 荻野肇

  2013, 日本動物学会大会予稿集, 84th


• Functional analysis of the histone H3K27 methyltransferase and demethylase in Xenopus embryonic development

  Akane Kawaguchi, Haruki Ochi, Norihiro Sudou, Makoto Okano, Hajime Ogino

  Nov. 2010, DIFFERENTIATION, 80, S28 - S28, English

  Summary international conference


• Evolution of a fail-safe regulatory system for kidney development

  Haruki Ochi, Chihiro Uchiyama, Akane Kawaguchi, Hajime Ogino

  Nov. 2010, DIFFERENTIATION, 80, S27 - S27, English

  Summary international conference


• Developmental switch of primary sensory system from Rohon-Beard cells to Dorsal root ganglia

  Kiyoshi Kawakami, Hiroshi Yajima, Makoto Suzuki, Haruki Ochi, Keiko Ikeda, Shigeru Sato, Hajime Ogino, Naoto Ueno

  Aug. 2010, DEVELOPMENTAL BIOLOGY, 344(1) (1), 531 - 531, English

  Summary international conference

• 水生動物はどのように腎を再生するのか ― 進化・比較から見る遺伝子発現制御の視点 ―

  第42回関西おさかな勉強会, Mar. 2026

  [Invited]

  Public discourse


• 腎再生における遺伝子発現調節とその進化メカニズム

  越智 陽城

  超階層生物学 JOINT WORKSHOP 2025 分子から形態形成、神経基盤から多様な繁殖行動にいたる超階層生物学, Mar. 2025

  Nominated symposium


• Regulation of shh limb enhancer (MFCS1) activity and its association with DNA methylation in Xenopus limb regeneration.

  Chifuyu Yokoyama, Reimi Tada, Takuya Higashidate, Takanori Amano, Saki Nara, Akane Kawaguchi, Nayuta Yakushiji, Haruki Ochi, Hajime Ogino, Joe Sakamoto, Yasuhiro Kamei, Koji Tamura, Hitoshi Yokoyama

  1st Asian Xenopus Conference, Nov. 2024, English

  Poster presentation


• The Role of Regeneration-Specific Promoters in Kidney Regeneration

  Haruki Ochi, Akane Kawaguchi

  1st Asian Xenopus Conference, Nov. 2024, English

  Poster presentation


• 細胞特異的レポーターをもつアフリカツメガエル作製の試み

  平山 一葉, 越智 陽城, 福井 彰雅

  日本動物学会 第95回長崎大会, Sep. 2024, Japanese

  Poster presentation


• Mechanisms of Reactivation of Developmental genes in Kidney Regeneration

  越智陽城

  シンポジウム 水生動物から考える発生・再生・進化における核内イベントの役割 第95回日本動物学会 長崎大会, Sep. 2024

  Nominated symposium


• Kidney Regeneration: Reactivation of Developmental Genes Through Enhancer Action

  Haruki Ochi

  International Zebrafish Conference 2024, Aug. 2024, English

  Poster presentation


• 腎再生における発生制御遺伝子の再活性化メカニズム

  ミニシンポジウム 東北地方の動物学の現状と将来 (東北大学浅虫海洋生物学教育研究センター), Feb. 2024

  Oral presentation


• Elucidate the Evolutionary Process Underlying Regenerative Capacity Loss

  越智陽城

  シンポジウム 水棲動物のゲノム科学で進化の謎を紐解く, オーガナイザー：大森義裕、荻野由紀子、第46回日本分子生物学会年会, 2023

  Invited oral presentation


• Unraveling the Mechanisms of Kidney Regeneration through Damage-Response/Regeneration Enhancers,

  Ochi H., Suzuki N.

  19th International Xenopus Conference., 2023

  Oral presentation


• クロマチンダイナミクスの解析から再生特異的なエンハンサーの活性化メカニズムに迫る

  鈴木 菜花, 荻野 肇, 越智 陽城

  日本動物学会 第91回大会 2020, Sep. 2020

  Nominated symposium


• The regulation of kidney regeneration: mechanisms of regeneration signal-response enhancer action

  Haruki Ochi

  Xenopus Resources and Emerging Technologies Meeting, Aug. 2019, English

  [Invited]

  Invited oral presentation


• Arid3a regulates nephric tubule regeneration through the evolutionarily conserved regeneration signal-response enhancer.

  Haruki Ochi

  52th Annual Meeting of the Japanese Society of Developmental Biologists,, May 2019, English

  Public symposium


• 再生シグナル応答エンハンサー ~活性化メカニズムと進化的保存性の意味~

  動物学会関東支部大会 公開シンポジウム 挑戦する両生類: カエル・イモリを使った研究の最前線, Mar. 2019, Japanese

  [Invited]

  Nominated symposium


• The regulation of kidney regeneration: mechanisms of regeneration signal-response enhancer action.,

  Ochi H.

  Xenopus Resources and Emerging Technologies Meeting 2019, 2019

  Invited oral presentation


• 二倍体と四倍体のカエルのゲノムに刻まれたシス調節配列から遺伝子発現調節の進化を読み解く

  越智 陽城

  第89回日本遺伝学会 (ワークショップ: 遺伝子重複は生物進化になにをもたらしたのか？), Sep. 2017


• 二倍体と四倍体のカエルのゲノムに刻まれた遺伝子発現調節の進化

  越智 陽城

  日本動物学会北海道支部講演会, Aug. 2017


• 脊椎動物の全ゲノム倍加と遺伝子発現調節メカニズムの進化

  越智 陽城

  弘前大学農学生命科学部 第14回研究推進セミナー, Jan. 2017


• 両生類のゲノム情報を利用したゲノム倍化後の遺伝子発現調節メカニズムの進化の研究

  越智 陽城

  国立遺伝学研究所ワークショップ 次世代モデル生物におけるゲノム情報利用ワークショップ,, Nov. 2016


• 再生シグナルに応答する非コードDNA領域から迫る再生を可能とさせる転写制御メカニズムの理解

  越智 陽城

  第121回日本解剖学会総会 (再生研究の新機軸 -不可能を可能とする内在性プログラムの探索-), Mar. 2016


• Have Mammals Lost the Regenerative Ability though the Loss of Regeneration Signal Response Elements?

  Ochi H., Suzuki N., Ogino H.

  NIBB, International Meeting on Aquatic Model Organisms for Human Disease and Toxicology Research,, 2016

  Nominated symposium


• 全ゲノム倍化直後の脊椎動物胚の遺伝子発現動態 (ワークショップ

  越智 陽城

  第37回日本分子生物学会 (ワークショップ: 生態進化発生学 (Eco-Evo-Devo)とは言うけども), Dec. 2015


• Identification of a cis-regulagory module for glomerular regeneration using comparative genomics and transgenesis techniques for amphibian.

  越智 陽城

  第85回日本動物学会 (ワークショップ: ゲノム情報と胚誘導形態形成研究のクロストーク), Sep. 2015


• Genome duplications and evolution of gene expression - What can artificial genome duplicated vertebrate embryos tell us about WGDs? –.

  越智 陽城

  日本進化学会第17回大会 (ワークショップ: Genome duplication: integrating comparative genomics population genetics, and experimentally synthesised polyploids), Sep. 2015


• 両生類のゲノム情報とトランスジェニックシステムを利用した再生に応答するゲノム領域の解析

  越智 陽城

  第86回日本動物学会 (ワークショップ: 新たな兆し~ネッタイツメガエル・アフリカツメガエルの研究舞台より), Sep. 2015


• 再生シグナル応答エンハンサーの活性化メカニズムから探る. 組織再生の理解

  越智 陽城

  次世代両生類研究会第1回会合, Aug. 2015


• Gene expression dynamics in the artificially genome duplicated vertebrate embryo.

  越智 陽城

  第86回日本遺伝学会 (ゲノム編集技術と両生類遺伝学の最先端, オーガナイザー), Sep. 2014


• ゲノム倍化によるシス調節機構の進化

  越智 陽城

  日本進化学会第14回大会 (ワークショップ: 遺伝子発現の相互作用と進化), Aug. 2012


• Molecular mechanisms underlying skeletal muscle development in zebrafish

  越智 陽城

  (国立遺伝学研究 ゼブラフィッシュの器官形成とイメージング, Aug. 2007

• THE MOLECULAR BIOLOGY SOCIETY OF JAPAN


• THE ZOOLOGICAL SOCIETY OF JAPAN


• JAPANESE SOCIETY OF DEVELOPMENTAL BIOLOGISTS


• 日本ツメガエル研究会


• International Zebrafish Society


• International Society for Regenerative Biology

• 瘢痕を残さない再生を導くスプライシング制御機構の解明

  公益財団法人 小柳財団, 2026 - 2026


• 組織再生を駆動する代謝再構築の原理

  公益財団法人 内藤記念科学振興財団, 2025 - 2026


• ナショナルバイオリソースプロジェクト・ツメガエル・イモリ 第5期

  荻野 肇, 加藤 尚志, 越智 陽城

  文部科学省 研究開発施設共用等促進費補助金ナショナルバイオリソースプロジェクト, 2022 - 2026, Coinvestigator


• パイオニア転写因子による再生エンハンサーのプライミング機構

  越智陽城

  日本学術振興会, 科学研究費助成事業 基盤研究(C), Apr. 2022 - Mar. 2025, Principal investigator


• スーパーエンハンサーによるオオノログ進化運命の拘束機構の研究

  荻野 肇, 越智 陽城, 井川 武

  日本学術振興会, 科学研究費助成事業 基盤研究(C), Apr. 2022 - Mar. 2025, Coinvestigator


• ネジル化修飾を介した PMLボディの凝集と腎組織再生促進の研究

  越智 陽城

  公益財団法人ノバルティス科学振興財団, Mar. 2023 - Apr. 2024


• 令和4年度 中核的拠点整備プログラム（ゲノム情報等整備・基盤技術整備）

  荻野 肇, 井川 武, 加藤 尚志, 越智 陽城

  文部科学省 研究開発施設共用等促進費補助金ナショナルバイオリソースプロジェクト, Sep. 2023 - Mar. 2024, Coinvestigator


• 再生遺伝子KLFの標的因子のPMLボディ集積の意義

  越智 陽城

  上原記念生命科学財団 研究助成金, Jan. 2023 - Mar. 2024, Principal investigator


• Analysis of evolutionary fate determination mechanisms of developmental genes after genome duplication events

  荻野 肇, 越智 陽城, 井川 武

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Hiroshima University, Apr. 2019 - Mar. 2022, Coinvestigator

  まずアフリカツメガエルが持つngn2の倍加遺伝子ペアに対してCRISPR/Cas9法を用いて遺伝子破壊を試みた。その結果、片方のコピーの破壊には成功したが、もう片方のコピーは実験条件をどのように変更しても表現型解析に十分な効率で破壊することができなかった。しかしこの実験の過程で、アフリカツメガエルの遺伝子破壊を最大効率化する方法を発見した（Tanouchi, M. et al., Dev. Growth Differ., 2022）。 一方、これまでの多くのゲノム重複研究は、遺伝子を機能で分類して、どのようなグループが倍加後も２コピーで維持されやすいか、あるいはシングルトン化しやすいかの傾向を調べることに留まってきた。本研究では、遺伝子の構造が進化運命に与える影響を抽出するため、倍加後も２コピーで維持されやすい転写制御因子の遺伝子群に注目し、祖先型２倍体ゲノムを持つネッタイツメガエルの遺伝子と、それに対する4倍体ゲノムを持つアフリカツメガエルのオーソログのペア885組を対象として解析を進めた。これらにおいて、アフリカツメガエルにおいて２コピーで維持されているものと、シングルトン化しているものの数を調べたところ、それぞれ783組（88%）と102組（12%）であった。さらにエンハンサー結合因子p300及びエンハンサーマークとして知られるヒストン修飾H3K4me1に対する抗体を用いたChIP-seqデータを用いて、それぞれのオーソログ組のネッタイツメガエル遺伝子が持つエンハンサーを同定し、その数を数えたところ、アフリカツメガエルにおいて２コピーで維持されている遺伝子に対するネッタイツメガエルオーソログの方が、アフリカツメガエルでシングルトン化している遺伝子に対するネッタイツメガエルオーソログよりも、エンハンサーの数が統計的に有意に多いことが明らかになった。


• Landscape of enhancer for nephric tubule regeneration

  Ochi Haruki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Yamagata University, Apr. 2019 - Mar. 2022

  We first collected proximal and intermediate tubules from Xenopus Pax8:GFP positive uninjured (day 0), regenerating (day 2), and regenerated (day 5) conditions for ATAC-seq and H3K27ac ChIP-seq, and uninjured (day 0), uninjured (day 2), and regenerating (day 2) conditions for RNA-seq. We then obtained putative enhancers of regeneration based on these data sets. In vivo enhancer activities for putative enhancers were tested using Xenopus transgenic system and confirmed that putative enhancers were activated after the injury of nephric tubules. Then, we applied the HOMER tools to identify drivers of the regeneration enhancers. We found a robust enrichment of Pbx, Tead, Klf motifs in regenerating specific open chromatin elements. Transcriptional activities were tested using luciferase reporter system, and Klf functions as an activator for these elements. These results suggest that the transcriptional activator of Klfs is one of the regulators for nephric tubules regeneration enhancers.


• ナショナルバイオリソースプロジェクト・ネッタイツメガエル 第4期

  荻野 肇, 加藤 尚志, 越智 陽城

  国立研究開発法人日本医療研究開発機構, 2021 - 2021, Coinvestigator


• DNAメチル化を指標とした両生類の生物学的年齢表の作成

  越智 陽城

  成茂動物科学振興基金, 2020 - 2021


• モデル動物等研究コーディネーティングネットワークによる希少・未診断疾患の病因遺伝子変異候補の機能解析研究 (分担)

  2020 - 2020


• 脊椎動物の上陸に伴う四肢での細胞死システムの確立

  田中幹子

  日本学術振興会, 基盤研究 (B), 2017 - 2019

  Competitive research funding


• 深層学習による疾患の超早期発見を可能にする病態発症前モデルの大規模スクリーニンク

  道上達男

  日本学術振興会, 基盤研究 (B) 特設領域 複雑系疾病論, 2017 - 2019

  Competitive research funding


• 腎尿細管再生のライブイメージングによる幹細胞の同定と再生促進剤の創出への展

  越智陽城

  公益財団法人 鈴木謙三記念医科学応用研究財団, 2017 - 2018, Principal investigator

  Competitive research funding


• 再生に応答して活性化するゲノム領域から迫る再生能を失うまでの進化プロセスの解明

  越智陽城

  日本学術振興会, 基盤研究 (C), 2016 - 2018, Principal investigator

  Competitive research funding


• ゲノム編集技術を使った新規研究モデル動物のリソース化拠点の形成

  越智陽城

  山形大学先進的研究拠点, YU-COE(C), 2014 - 2018, Principal investigator

  Competitive research funding


• 体内受精様式の成立に関わる輸卵管の機能進化の実証的研究

  渡辺絵里子

  日本学術振興会, 基盤研究 (C), 2015 - 2017

  Competitive research funding


• 腎臓再生の三次元イメージングによる再生原理の解明

  越智 陽城

  日本学術振興会, 科学研究費助成事業, 新学術領域研究(研究領域提案型), 山形大学, 01 Apr. 2013 - 31 Mar. 2016

  ほ乳類の腎組織は、ひとたび損傷を受けるとその機能を再生するのは極めて難しい。一方、両生類や魚類のなかには、生体内で腎組織を再生できるものがあり、この再生能力を支える分子機構を応用すれば、ヒトにおいても腎臓などの複雑な組織や器官を再生できるようになると期待される。これまでの発生再生学的な研究から、再生で使われる多くの遺伝子は、発生過程で使われるものが再利用されていることが知られている。本研究は、両生類の腎再生過程で働く遺伝子の発現調節メカニズムをほ乳類などの再生能が限られた動物と比較し、ネフロン再構築の遺伝子ネットワークの全体像を捉えることを目的としたものである。これまでに魚類の腎再生過程で発現が上昇することがしられているLhx1、Six2、Pax2、Pax8の保存非コードDNA領域について、両生類のトランスジェニックエンハンサーマッピングシステムと外科的切除による再生実験を組み合わせ、ツメガエルのそれら遺伝子座近傍で、発現を活性化する再生シグナル応答エンハンサーを同定してきた。本年度は、それらを腎再生が可能な魚類と両生類の間のみで保存されている領域と、再生能が限られているほ乳類においてもその相同配列が保存されている領域に着目し比較解析を行なったところ、両生類の前腎再生組織で強いエンハンサー活性を示す領域は、ほ乳類においても進化的に保存されている領域であることがわかった。次に、マウスの相同領域を用いてトランスジェニックレポーター解析を行なったところ、マウスのゲノム中にも両生類の前腎の再生過程で働くエンハンサーが存在することがわかった。これらの結果は、両生類や魚類と比べほ乳類の再性能が限られている要因は、再生で働く再生シグナル応答エンハンサーとその制御下にある遺伝子が失われたというよりも、エンハンサー活性を抑制するメカニズムが進化の過程で獲得されたことを示唆している。


• 越智陽城

  科学技術振興機構, テニュアトラック普及･定着事業 (個人選抜型), 2013 - 2016, Principal investigator

  Competitive research funding


• 脊椎動物の人工ゲノム倍化によるアダプテーション原理の解明

  越智 陽城

  日本学術振興会, 科学研究費助成事業, 新学術領域研究(研究領域提案型), 山形大学, 01 Apr. 2013 - 31 Mar. 2015

  脊椎動物は進化の過程で遺伝子とその発現を調節するシス配列 (エンハンサーやサイレンサー)が倍増する全ゲノム重複を２回経験した。これにより遺伝子回路が高度化し、私たちの発達した臓器や脳、それに起因する複雑な生理特性と行動がもたらされたと考えられている。しかしながら、脊椎動物の進化の鍵となる全ゲノム倍化が起きたとき、ゲノムに何がおきたのか、遺伝子の発現状態やそのシス調節配列がどのように働いたのかは全くわかっていない。この問題は、現存する動物のゲノム配列を比較するだけでは永遠に解決し得ず、ゲノム配列に進化の痕跡を求めるのではなく、倍化を人工的に再現し、進化の初期状態を観察する必要がある。本研究は、脊椎動物なかでも容易にゲノムを倍化させることができるネッタイツメガエルを用いて、倍化直後の遺伝子発現の動態とエピゲノム状態を解析することで、脊椎動物の進化の初期になにが起きたのか解明することを目的としている。昨年度までに、2倍体胚と比べて、正常に発生した倍化体胚で1,779遺伝子の発現の減少がみられ、発現の亢進がみられたものは514遺伝子であった。これらの発現変動がみられた遺伝子のなかには、発生制御遺伝子は含まれていないことを明らかにしていた。今年度は、倍化体の個体サイズや核のサイズを測定した結果、2倍体胚と4倍体胚でほとんど変わらない事を明らかにした。これらの結果は、脊椎動物の全ゲノム倍化直後の胚で正常に発生する個体は、発生制御遺伝子の発現量のバランス調節や個体サイズの調整が起きていることを示唆するものである。


• パラログ遺伝子間クロストークによる遺伝子発現の安定化機構

  越智陽城

  日本学術振興会, 若手研究 (B), 2012 - 2014, Principal investigator

  Competitive research funding


• ゲノムアダプテーションのシステム的理解 公募班

  日本学術振興会, 2012 - 2013


• Pax2塩濃度感知型エンハンサーの加齢によるエピゲノム変化と慢性腎臓疾患の発症の相関に関する研究

  越智陽城

  岸本基金研究助成公益財団法人 千里ライフサイエンス振興財団, 2012 - 2013, Principal investigator

  Competitive research funding


• 越智陽城

  日本学術振興会, 新学術領域 三次元構造を再構築する再生原理の解明 公募班, 2012 - 2013, Principal investigator

  Competitive research funding


• Molecular mechanisms and evolutionary origin of the robustness in vertebrate development

  OGINO HAJIME, OCHI Haruki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), 2011 - 2013

  In this study, we attempted to reveal molecular mechanisms that confer robustness to vertebrate development, and its evolutionary origin, by studying the regulation of paralogs generated by ancient whole genome duplications. In case of Nr2f-paralogs, we found that Nr2f1, Nr2f2, Nr2f5 and Nr2f6, show partially overlapping expression in the eye and brain, and three pairs of enhancers generated by the genome duplication are still conserved between Nr2f1 and Nr2f2. Regarding Pax2 and Pax5 paralogs, an ancestral-type sequence of their expression-compensation enhancers was identified in the cephalochordate amphioxus.


• 両生類と哺乳類の種差に基づいた再生エンハンサーの機能解析

  越智陽城

  公益財団法人 武田科学振興財団 ライフサイエンス研究奨励, 2012, Principal investigator

  Competitive research funding


• Femtosecond laser-introduction of bionanomolecules in targeted single cells of living vertebrate embryos

  TANAKA Mikiko, HOSOKAWA Yohichiro, OCHI Haruki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Challenging Exploratory Research, Tokyo Institute of Technology, 2010 - 2011

  Introduction of biomolecules into cells in living animals is one of the most important techniques in molecular and developmental biology research, and has potentially broad biomedical implications. Here we report that biomolecules can be introduced into single cells in living vertebrate embryos by photoporation using a femtosecond laser amplifier with a high pulse energy and a low repetition rate. First, we confirmed the efficiency of this photoporation technique by introducing dextran, morpholino oligonucleotides, or DNA plasmids into targeted single cells of zebrafish, chick, and shark embryos. Second, we demonstrated that femtosecond laser irradiation efficiently delivered DNA plasmids into single neurons of chick embryos. Finally, we successfully manipulated the fate of single neurons in zebrafish embryos by delivering mRNA. Our observations suggest that photoporation using a femtosecond laser with a high pulse energy and low repetition rate offers a novel way to manipulate the function(s) of individual cells in a wide range of vertebrate embryos by introduction of selected biomolecules.


• Genome-wide mapping of cis-regulatory elements conserved in vertebrates

  OGINO Hajime, OCHI Haruki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project), Nara Institute of Science and Technology, 2009 - 2011

  We performed cis-regulatory analyses of genes involved in development and disease in a genome-wide manner, using comparative genomics approach and an efficient transgenesis technique in Xenopus. Conserved enhancers were identified in a variety of genes including Pax family and Polycomb-related genes. Furthermore, comparative functional analysis between the vertebrate and amphioxus cis-regulatory elements revealed that silencer innovation, rather than enhancer degeneration, was crucial for the diversification of paralog expression during vertebrate evolution.


• パラログ遺伝子のシス調節配列の進化と遺伝子ネットワークのフェイルセーフ機構の解析

  越智陽城

  日本学術振興会, 若手研究 (B), 2009 - 2011, Principal investigator

  Competitive research funding


• 水中から陸上へ _ Pax2遺伝子のシス調節配列の進化による中耳獲得メカニズムの研究

  越智陽城

  公益財団法人 稲盛財団, 2009 - 2010, Principal investigator

  Competitive research funding


• The search for new developmental genes using a gene trap approach in Xenopus tropicalis

  OGINO Hajime, OCHI Haruki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Nara Institute of Science and Technology, 2008 - 2010

  In this study, we attempted a gene trap mutagenesis in Xenopus tropicalis to identify new developmental regulatory genes, using a high-throughput transgenesis technique that we developed recently. The random insertion of a newly designed gene trap vector into the Xenopus genome resulted in generation of an albino mutant, which showed that insertional mutagenesis is actually feasible in Xenopus tropicalis.


• 多発性嚢胞腎症の原因遺伝子PKDによるPax2遺伝子の発現調節機構の解明

  越智陽城

  日本科学財団 笹川科学助成金, 2009, Principal investigator

  Competitive research funding


• 多発性嚢胞腎症の治療薬開発を支援するPKDシグナル活性評価法の開発

  越智陽城

  科学技術振興機構, シーズ発掘試験, 2009, Principal investigator

  Competitive research funding

• アドレナリン受容体作動薬で両生類の腎尿細管再生を促進

  科学新聞, 22 Sep. 2022


• 水かきの有無 酸素が鍵 日米チーム発見

  朝日新聞, Aug. 2019


• 複雑なカエルゲノム解読 進化の謎、解明に期待

  神戸新聞NEXT, Oct. 2016


• 複雑なカエルゲノム解読 山形大学医学部越智准教授ら国際チーム発表

  山形新聞, Oct. 2016


• 重複遺伝子 オフにして進化

  産経新聞, May 2012


• 「オフ」スイッチで進化 先端大 解明 遺伝子「オン」消去

  奈良新聞, May 2012


• 遺伝子抑制 進化に貢献 ナメクジウオで解明

  毎日新聞, May 2012