Analysis of the regulatory mechanism of epigenetic factors in retinal cell differentiation

• Project/Area Number: 19H03420
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: Omori Yoshihiro 長浜バイオ大学, バイオサイエンス学部, 教授 (90469651)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 網膜 / 脊椎動物 / ゲノム進化 / 脊椎動物モデル / エピジェネティクス / シングルセル解析 / 網膜変性疾患 / 視細胞 / 動物モデル

Outline of Research at the Start

私たちの眼球に入射した映像は、まず網膜の神経回路により受容、処理される。この網膜神経回路を構成するニューロンとグリアはサブタイプを含めると約70種類以上に及ぶ。また、網膜視細胞にはシナプスや繊毛が発達し、視覚情報の取得に重要な役割を果たしている。近年、網膜においてエピゲノム変化の網羅的解析が進み、網膜細胞の多様性を確立する過程には、クロマチン状態の変化を伴うことが解明されつつあるが、その制御因子やメカニズムの実体の解明は進んでいない。本課題では脊椎動物モデルを用いて網膜におけるエピジェネティック制御機構の解析を行い、中枢神経の発生と機能に重要なメカニズムの解明を目指す。

Outline of Final Research Achievements

Images that we observed using the eyes are first received and processed by neural circuits in the retina. There are more than 70 types of neurons and glia in the retinal neural circuit. In addition, retinal photoreceptor cells have well-developed synapses and cilia, which play an important role in the acquisition of visual information. Recently, a comprehensive analysis of epigenomic changes in the retina has revealed that the process of establishing retinal cell diversity is accompanied by changes in chromatin state, however the regulatory mechanisms have not been elucidated yet. We analyze the epigenetic control mechanisms in the retina using vertebrate models. We will elucidate the mechanisms important for the development and function of the central nervous system.

Academic Significance and Societal Importance of the Research Achievements

変異体キンギョやゲノム編集による遺伝子改変ゼブラフィッシュや遺伝子改変マウスなどの脊椎動物モデルを用いて、網膜の細胞分化におけるエピジェネティック因子による制御機構の解析を行うことで、脊椎動物における網膜の発生と維持の分子メカニズムの解明に繋げることができる。これらの研究から得られた脊椎動物の網膜における生物学的な知見により発生や進化などの基礎生物学的な理解の蓄積に繋がる。これらの基礎生物学的な知識は、基礎医学の分野でも重要であり、眼科領域疾患の治療法や診断法の確立に貢献することが期待される。

Research Products

• [Int'l Joint Research] NIH(米国)
• [Int'l Joint Research] NIH(米国)
• [Int'l Joint Research] NIH(米国)
• [Journal Article] Whole-genome resequencing of large yellow croaker (Larimichthys crocea) reveals the population structure and signatures of environmental adaptation (2021)
  • Author(s): Kon Tetsuo、Pei Liyi、Ichikawa Ryota、Chen Chunyan、Wang Ping、Takemura Ikuyo、Ye Yingying、Yan Xiaojun、Guo Baoying、Li Weiye、Lauden Hagai Nsobi、Tabata Hiromasa、Pan Hao、Omori Yoshihiro、Ogura Atsushi、Jiang Lihua
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 11235-11235
  • DOI: 10.1038/s41598-021-90645-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Whole-genome sequencing of endangered Zhoushan cattle suggests its origin and the association of MC1R with black coat colour (2021)
  • Author(s): Jiang Lihua、Kon Tetsuo、Chen Chunyan、Ichikawa Ryota、Zheng Qiyuan、Pei Liyi、Takemura Ikuyo、Nsobi Lauden Hagai、Tabata Hiromasa、Pan Hao、Omori Yoshihiro、Ogura Atsushi
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 17359-17359
  • DOI: 10.1038/s41598-021-96896-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional analysis of Samd11, a retinal photoreceptor PRC1 component, in establishing rod photoreceptor identity (2021)
  • Author(s): Kubo Shun、Yamamoto Haruka、Kajimura Naoko、Omori Yoshihiro、Maeda Yamato、Chaya Taro、Furukawa Takahisa
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 4180-4180
  • DOI: 10.1038/s41598-021-83781-1
  • Peer Reviewed / Open Access
• [Journal Article] 連載講座 生命科学を拓く新しい実験動物モデル−20 キンギョの多様な表現型と全ゲノム重複-疾患モデル動物としての展開 (2020)
  • Author(s): 大森 義裕
  • Journal Title: 生体の科学 Volume: 71 Issue: 1 Pages: 68-73
  • DOI: 10.11477/mf.2425201122
  • ISSN: 0370-9531, 1883-5503
  • Year and Date: 2020-02-15
• [Journal Article] Functional and Evolutionary Diversification of Otx2 and Crx in Vertebrate Retinal Photoreceptor and Bipolar Cell Development. (2020)
  • Author(s): 5).Yamamoto H, Kon T, Omori Y, Furukawa T
  • Journal Title: Cell Reports30 Volume: 30 Issue: 3 Pages: 658-671.e5
  • DOI: 10.1016/j.celrep.2019.12.072
  • Peer Reviewed / Open Access
• [Journal Article] Anterograde trafficking of ciliary MAP kinase?like ICK/CILK1 by the intraflagellar transport machinery is required for intraciliary retrograde protein trafficking (2020)
  • Author(s): Nakamura Kentaro、Noguchi Tatsuro、Takahara Mariko、Omori Yoshihiro、Furukawa Takahisa、Katoh Yohei、Nakayama Kazuhisa
  • Journal Title: Journal of Biological Chemistry Volume: 295 Issue: 38 Pages: 13363-13376
  • DOI: 10.1074/jbc.ra120.014142
  • Peer Reviewed / Open Access
• [Journal Article] The Genetic Basis of Morphological Diversity in Domesticated Goldfish (2020)
  • Author(s): Kon Tetsuo、Omori Yoshihiro、Fukuta Kentaro、Wada Hironori、Watanabe Masakatsu、Chen Zelin、Iwasaki Miki、Mishina Tappei、Matsuzaki Shin-ichiro S.、Yoshihara Daiki、Arakawa Jumpei、Kawakami Koichi、Toyoda Atsushi、Burgess Shawn M.、Noguchi Hideki、Furukawa Takahisa
  • Journal Title: Current Biology Volume: 30 Issue: 12 Pages: 2260-2274.e6
  • DOI: 10.1016/j.cub.2020.04.034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular mechanisms underlying selective synapse formation of vertebrate retinal photoreceptor cells. (2020)
  • Author(s): Furukawa T, Ueno A, Omori Y
  • Journal Title: Cell Mol Life Science Volume: 77 Issue: 7 Pages: 1251-1266
  • DOI: 10.1007/s00018-019-03324-w
  • Peer Reviewed / Open Access
• [Journal Article] De novo assembly of the goldfish (Carassius auratus) genome and the evolution of genes after whole-genome duplication (2019)
  • Author(s): Chen Zelin、Omori Yoshihiro、Koren Sergey、Shirokiya Takuya、Kuroda Takuo、Miyamoto Atsushi、Wada Hironori、Fujiyama Asao、Toyoda Atsushi、Zhang Suiyuan、Wolfsberg Tyra G.、Kawakami Koichi、Phillippy Adam M.、Mullikin James C.、Burgess Shawn M.、NISC Comparative Sequencing Program
  • Journal Title: Science Advances Volume: 5 Issue: 6
  • DOI: 10.1126/sciadv.aav0547
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation. (2019)
  • Author(s): Kozuka T, Omori Y, Watanabe S, Tarusawa E, Yamamoto H, Chaya T, Furuhashi M, Morita M, Sato T, Hirose S, Ohkawa Y, Yoshimura Y, Hikida T, Furukawa T.
  • Journal Title: Sci Rep. Volume: Mar 5;9(1) Issue: 1 Pages: 3445-3445
  • DOI: 10.1038/s41598-019-38910-2
  • NAID: 120006579467
  • Peer Reviewed / Open Access
• [Presentation] キンギョ(Carassius auratus)とその近縁種、そして全ゲノム重複後の進化 (2021)
  • Author(s): Yoshihiro Omori,Tetsuo Kon, Kentaro Fukuta, Mari Nishino, Natsuki Noda, Atsushi Toyoda, Hideki Noguchi
  • Organizer: 第44回 日本分子生物学会年会
  • Int'l Joint Research / Invited
• [Presentation] Diversity of morphological phenotypes in domesticated goldfish strains and their whole genome analysis (2021)
  • Author(s): Yoshihiro Omori,Tetsuo Kon, Kentaro Fukuta, Atsushi Toyoda, Hideki Noguchi
  • Organizer: The 2nd Asia Evo Conference 2021
  • Int'l Joint Research / Invited
• [Presentation] 公開講演会「今!キンギョがおもしろい」 (2021)
  • Author(s): 大森義裕
  • Organizer: 日本動物学会 中部支部会
  • Invited
• [Presentation] Mechanism of the eye size control using the Demekin strain of goldfish (Carassius auratus) (2021)
  • Author(s): Yoshihiro Omori,Tetsuo Kon, Kentaro Fukuta, Atsushi Toyoda, Hideki Noguchi
  • Organizer: 2021年 日本生化学会大会
  • Int'l Joint Research / Invited
• [Presentation] Understanding of molecular mechanisms underlying on morphological diversity of goldfish (Carassius auratus) strains (2020)
  • Author(s): Tetsuo Kon, Yoshihiro Omori
  • Organizer: 日本分子生物学会大会
  • Invited
• [Presentation] A data-scientific approach toward understanding of the goldfish genome and morphological diversity (2020)
  • Author(s): Tetsuo Kon, Yoshihiro Omori
  • Organizer: International Symposium: Global Collaboration on Data beyond Disciplines
  • Int'l Joint Research / Invited
• [Presentation] 組織特異的ポリコーム抑制複合体1(PRC1)の構成要素Samd7は網膜桿体視細胞のアイデンティティーの確立に重要である (2019)
  • Author(s): 大森義裕、久保竣、今鉄男、成田宏隆、上野明希子、堤崚太郞、茶屋太郎、山本悠、中川敦史、古川貴久
  • Organizer: 第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会 合同年次大会
  • Invited
• [Presentation] キンギョ品種の形態形成を制御するメカニズムの解析 (2019)
  • Author(s): YOSHIHIRO OMORI, Tetsuo Kon, Kentaro Fukuta, Hironori Wada, Masakatsu Watanabe, Zelin Chen, Koichi Kawakami, Takahisa Furukawa, Hideki Noguchi, Shawn Burgess, Atsushi Toyoda
  • Organizer: 第52回 日本発生生物学会大会
• [Presentation] キンギョの全ゲノム配列決定と品種に見られる多様な表現型を規定する遺伝子の探索 (2019)
  • Author(s): YOSHIHIRO OMORI, Tetsuo Kon, Kentaro Fukuta, Zelin Chen, Hironori Wada, Masakatsu Watanabe, Hideki Noguchi, Asao Fujiyama, Atsushi Toyoda, Koichi Kawakami, Shawn Burgess, Takahisa Furukawa
  • Organizer: 第42回 日本分子生物学会年会
  • Invited
• [Presentation] Goldfish genome resequencing and the phenotypic variations of domesticated strains (2019)
  • Author(s): Yoshihiro Omori, Tetsuo Kon, Kentaro Fukuta, Hironori Wada, Masakatsu Watanabe, Zelin Chen, Koichi Kawakami, Takahisa Furukawa, Atsushi Toyoda, Shawn Burgess, Hideki Noguchi
  • Organizer: The 14th International Zebrafish Conference
  • Int'l Joint Research
• [Book] zebrafish: The genetics and genome analysis of domesticated goldfish strains with a wide variety of phenotypes (2022)
  • Author(s): Yoshihiro Omori
  • Total Pages: 17
  • Publisher: Springer Protocols
• [Remarks] 長浜バイオ大学大学院 大森研究室
  • URL: https://yoshihiroomori.web.fc2.com/