Morito, Satoru

写真a

Affiliation

School of Medicine, Division of Brain Sciences (Shinanomachi)

Position

Instructor
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Career 【 Display / hide 】

  • 2005.04
    -
    2009.03

    National Institute for Basic Biology・Postdoc

  • 2009.04
    -
    2009.10

    National Institute for Basic Biology・Postdoc

  • 2009.11
    -
    2012.05

    National Institute for Physiological Sciences・Postdoc

  • 2012.06
    -
    2012.09

    National Institute for Physiological Sciences・Postdoc

  • 2012.10
    -
    2015.03

    Tohoku University Graduate School of Medicine・Teaching Associate / Research Associate

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Academic Degrees 【 Display / hide 】

  • Doctor (Bioscience), Nara Institute of Science and Technology, Coursework, 2005.03

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Research Areas 【 Display / hide 】

  • Life Science / Genome biology

  • Life Science / Cell biology

  • Life Science / Developmental biology

  • Life Science / Neuroscience-general

  • Life Science / Ophthalmology

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Research Keywords 【 Display / hide 】

  • retina, pluripotent stem cell, ES/iPS cells, retinal cell differentiation, three-dimensional retinal tissue

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Books 【 Display / hide 】

  • 植物のエピジェネティクス（細胞工学別冊 植物細胞工学シリーズ24）・アサガオとイネのDNAメチル化と遺伝子発現

    定塚(久富)恵世, 星野敦, 森田裕将, 山内卓樹, 朴慶一, 寺田理枝, 森藤暁, 飯田滋, 秀潤社, 2008.04

    Scope: 36-43

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Papers 【 Display / hide 】

  • Synaptic pruning through glial synapse engulfment upon motor learning.

    Yosuke M Morizawa, Mami Matsumoto, Yuka Nakashima, Narumi Endo, Tomomi Aida, Hiroshi Ishikane, Kaoru Beppu, Satoru Moritoh, Hitoshi Inada, Noriko Osumi, Eiji Shigetomi, Schuichi Koizumi, Guang Yang, Hirokazu Hirai, Kohichi Tanaka, Kenji F Tanaka, Nobuhiko Ohno, Yugo Fukazawa, Ko Matsui

    Nature neuroscience 25 ( 11 ) 1458 - 1469 2022.11

    ISSN  1097-6256

    　View Summary

    Synaptic pruning is a fundamental process of neuronal circuit refinement in learning and memory. Accumulating evidence suggests that glia participates in sculpting the neuronal circuits through synapse engulfment. However, whether glial involvement in synaptic pruning has a role in memory formation remains elusive. Using newly developed phagocytosis reporter mice and three-dimensional ultrastructural characterization, we found that synaptic engulfment by cerebellar Bergmann glia (BG) frequently occurred upon cerebellum-dependent motor learning in mice. We observed increases in pre- and postsynaptic nibbling by BG along with a reduction in spine volume after learning. Pharmacological blockade of engulfment with Annexin V inhibited both the spine volume reduction and overnight improvement of motor adaptation. These results indicate that BG contribute to the refinement of the mature cerebellar cortical circuit through synaptic engulfment during motor learning.

  • Optogenetic stimulus-triggered acquisition of seizure resistance.

    Yoshiteru Shimoda, Kaoru Beppu, Yoko Ikoma, Yosuke M Morizawa, Satoshi Zuguchi, Utaro Hino, Ryutaro Yano, Yuki Sugiura, Satoru Moritoh, Yugo Fukazawa, Makoto Suematsu, Hajime Mushiake, Nobukazu Nakasato, Masaki Iwasaki, Kenji F Tanaka, Teiji Tominaga, Ko Matsui

    Neurobiology of disease 163   105602 - 105602 2022.02

    ISSN  0969-9961

    　View Summary

    Unlike an electrical circuit, the hardware of the brain is susceptible to change. Repeated electrical brain stimulation mimics epileptogenesis. After such "kindling" process, a moderate stimulus would become sufficient in triggering a severe seizure. Here, we report that optogenetic neuronal stimulation can also convert the rat brain to a hyperexcitable state. However, continued stimulation once again converted the brain to a state that was strongly resistant to seizure induction. Histochemical examinations showed that moderate astrocyte activation was coincident with resilience acquisition. Administration of an adenosine A1 receptor antagonist instantly reverted the brain back to a hyperexcitable state, suggesting that hyperexcitability was suppressed by adenosine. Furthermore, an increase in basal adenosine was confirmed using in vivo microdialysis. Daily neuron-to-astrocyte signaling likely prompted a homeostatic increase in the endogenous actions of adenosine. Our data suggest that a certain stimulation paradigm could convert the brain circuit resilient to epilepsy without exogenous drug administration.

  • DNA methylation is reconfigured at the onset of reproduction in rice shoot apical meristem.

    Asuka Higo, Noriko Saihara, Fumihito Miura, Yoko Higashi, Megumi Yamada, Shojiro Tamaki, Tasuku Ito, Yoshiaki Tarutani, Tomoaki Sakamoto, Masayuki Fujiwara, Tetsuya Kurata, Yoichiro Fukao, Satoru Moritoh, Rie Terada, Toshinori Kinoshita, Takashi Ito, Tetsuji Kakutani, Ko Shimamoto, Hiroyuki Tsuji

    Nature communications 11 ( 1 ) 4079 - 4079 2020.08

    　View Summary

    DNA methylation is an epigenetic modification that specifies the basic state of pluripotent stem cells and regulates the developmental transition from stem cells to various cell types. In flowering plants, the shoot apical meristem (SAM) contains a pluripotent stem cell population which generates the aerial part of plants including the germ cells. Under appropriate conditions, the SAM undergoes a developmental transition from a leaf-forming vegetative SAM to an inflorescence- and flower-forming reproductive SAM. While SAM characteristics are largely altered in this transition, the complete picture of DNA methylation remains elusive. Here, by analyzing whole-genome DNA methylation of isolated rice SAMs in the vegetative and reproductive stages, we show that methylation at CHH sites is kept high, particularly at transposable elements (TEs), in the vegetative SAM relative to the differentiated leaf, and increases in the reproductive SAM via the RNA-dependent DNA methylation pathway. We also show that half of the TEs that were highly methylated in gametes had already undergone CHH hypermethylation in the SAM. Our results indicate that changes in DNA methylation begin in the SAM long before germ cell differentiation to protect the genome from harmful TEs.

  • Gene delivery to cone photoreceptors by subretinal injection of rAAV2/6 in the mouse retina.

    Tesshu Hori, Masashi Fukutome, Chiseto Maejima, Hiroki Matsushima, Kensuke Kobayashi, Soichiro Kitazawa, Ryo Kitahara, Katsunori Kitano, Kenta Kobayashi, Satoru Moritoh, Chieko Koike

    Biochemical and biophysical research communications 515 ( 1 ) 222 - 227 2019.07

    　View Summary

    Adeno-associated virus (AAV) has been studied as a safe delivery tool for gene therapy of retinal blinding diseases such as Leber's congenital amaurosis (LCA). The tropism of recombinant AAV (rAAV) including its specificity and efficiency in targeting retinal cell types has been studied with native or engineered capsids, along with specific promoters. However, one of the rAAV serotypes, rAAV2/6, has not been well-studied based on a report of low infection efficiency in the retina. We investigated the tropism of several rAAVs by subretinal injection in the adult mouse and found that rAAV2/6 predominantly infected cone photoreceptors including the main spectral type. Our data suggest that subretinal injection with rAAV2/6 may provide both an efficacious and specific means of gene delivery to cone photoreceptors in murine retinas.

  • Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice.

    Haruki Takeuchi, Sho Horie, Satoru Moritoh, Hiroki Matsushima, Tesshu Hori, Yoshitaka Kimori, Katsunori Kitano, Yasuhiro Tsubo, Masao Tachibana, Chieko Koike

    BioMed research international 2018 ( Article ID 2963232 ) 2963232 - 2963232 2018

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    TRPM1, the first member of the melanoma-related transient receptor potential (TRPM) subfamily, is the visual transduction channel downstream of metabotropic glutamate receptor 6 (mGluR6) on retinal ON bipolar cells (BCs). Human TRPM1 mutations are associated with congenital stationary night blindness (CSNB). In both TRPM1 and mGluR6 KO mouse retinas, OFF but not ON BCs respond to light stimulation. Here we report an unexpected difference between TRPM1 knockout (KO) and mGluR6 KO mouse retinas. We used a multielectrode array (MEA) to record spiking in retinal ganglion cells (RGCs). We found spontaneous oscillations in TRPM1 KO retinas, but not in mGluR6 KO retinas. We performed a structural analysis on the synaptic terminals of rod ON BCs. Intriguingly, rod ON BC terminals were significantly smaller in TRPM1 KO retinas than in mGluR6 KO retinas. These data suggest that a deficiency of TRPM1, but not of mGluR6, in rod ON bipolar cells may affect synaptic terminal maturation. We speculate that impaired signaling between rod BCs and AII amacrine cells (ACs) leads to spontaneous oscillations. TRPM1 and mGluR6 are both essential components in the signaling pathway from photoreceptors to ON BC dendrites, yet they differ in their effects on the BC terminal and postsynaptic circuitry.

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Reviews, Commentaries, etc. 【 Display / hide 】

  • げっ歯類成熟網膜組織培養と遺伝子銃による遺伝子導入法(Organotypic culture of adult rodent retina with particle-mediated acute gene transfer in vitro)

    森藤 暁, 田中 謙二, 池中 一裕, 小泉 周

    神経化学 (日本神経化学会)  49 ( 2-3 ) 726 - 726 2010.08

    ISSN  0037-3796

  • Organotypic culture of adult rodent retina and gene transfection by genegun

    Hiroshi Jouhou, Satoru Moritoh, Amane Koizumi

    JOURNAL OF PHYSIOLOGICAL SCIENCES (SPRINGER TOKYO)  60   S108 - S108 2010

    ISSN  1880-6546

  • Organotypic culture of adult rodent retina with particle-mediated acute gene transfer in vitro

    Satoru Moritoh, Kenji F. Tanaka, Kazuhiro Ikenaka, Amane Koizumi

    NEUROSCIENCE RESEARCH (ELSEVIER IRELAND LTD)  68   E384 - E384 2010

    ISSN  0168-0102

  • Generation of rice knock-in mutants by gene targeting and preliminary characterization of the expression of targeted genes

    Takaki Yamauchi, Ric Terada, Yasuyo (Hisatomi) Johzuka, Satoru Moritoh, Ikuo Nakamura, Shigeru Iida

    PLANT AND CELL PHYSIOLOGY (OXFORD UNIV PRESS)  48   S91 - S91 2007

    ISSN  0032-0781

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 単純ヘルペスウイルスをトレーサーに用いた非視覚光受容体の近視抑制の脳内回路の同定

    2024.04
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    2027.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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    マウスにおいて、非視覚光受容体のOpn5が、バイオレットライト(360 - 400 nm)を介して近視進行を抑制することが明らかになったが、Opn5がどのような脳内回路を経て、眼軸長伸長の抑制や脈絡膜厚の維持など近視の抑制に働いているのかは、明らかになっていない。そこで、本研究では、国内のグループで開発された単純ヘルペスウイルスのBACを改変することにより、順行性の経シナプスの神経細胞トレーサーを開発し、Opn5陽性網膜神経節細胞からの脳内の神経回路網を明らかにすることを目的とする。本研究により、近視抑制の脳内回路の解明が進むことで、将来的な近視の予防や治療法の開発に貢献することが期待される。

  • RNA結合タンパク質Quakingによる網膜初期発生の分子機構の解明

    2020.04
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    2023.03

    Grants-in-Aid for Scientific Research, 森藤 暁, 小池 千恵子, 川村 晃久, Grant-in-Aid for Scientific Research (C), No Setting

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    RNA結合タンパク質Quaking(Qki)が、網膜前駆細胞とミュラーグリア細胞において強く発現しているが、網膜での機能は明らかになっていない。本研究では、ES細胞やiPS細胞といった多能性幹細胞からの3次元網膜分化法を網膜初期発生の迅速な遺伝子機能解析の実験系とすることで、網膜初期発生におけるQkiやQkiの標的遺伝子の役割を明らかにしたい。Qkiに着目した網膜初期発生の分子機構の解明により、網膜発生や分化の理解が深まることで、将来的に網膜分化系の改良など再生医療や創薬のための重要な基礎研究となることが期待される。
    CRISPR/Cas9法により、マウスES細胞株で、Qkiノックアウトクローンを1クローン単離することができた。タンパク質、DNAの回収を行い、ウエスタン解析・シークエンス解析によってQki遺伝子の破壊の確認を行ったところ、このクローンにおいてQkiのノックアウトが確認された。この株においては、細胞増殖能は、野生型と同様で、NanogやOct4といった幹細胞の未分化マーカーが発現していることから、この株は未分化維持されており、通常のES細胞と同様に増殖することが分かった。このQkiノックアウトクローンを3次元網膜に分化させたところ、初回は、網膜様構造への分化が停止するという表現型を得たが、2回目以降は、網膜様構造が観察され、野生型細胞が混入したためなのかなど、3次元網膜の表現型についてはっきりとした結論がだせていない。このため、別のQkiノックアウトクローンの単離を行うことにした。現在、別のQkiノックアウトクローンの単離中である。また、Qki KOマウスを理研BRCより入手した。Qki KOマウスは、胚性致死であるが、致死になるE9.5-E10.5における眼の表現型については報告されていないため、現在凍結切片により、E9.5でのQki KOマウスのホモ個体の眼について調査している。さらに、海外の研究者より、Qki floxマウスを取り寄せており、近日中にマウスの清浄化が終わるため、動物施設に搬入し、解析を開始する予定である。
    単離できたQkiノックアウトクローンの3次元網膜の表現型がはっきりと確定できなかったため、再度、Qkiノックアウトクローンを単離することにした。このため、研究進捗状況について、やや遅れていると判断した。
    引き続きQkiノックアウトクローンの単離を行う。もし、野生型とQkiノックアウトクローンについて、3次元網膜の表現型の差がみられるようであれば、Qki cDNAの過剰発現により、表現型が回復するかどうかを調べ、RNA-seq解析により、どのような遺伝子群の発現に差がみられるのかを解析する。Qki KOマウスについてE9.5でのQki KOマウスのホモ個体の眼の表現型の解析を実施する。さらに近日中に到着するQki floxマウスとDkk3-Creマウスを交配し、網膜前駆細胞で特異的にQkiを欠損させた網膜の表現型の解析を行う。

  • Development of purification method of photoreceptors differentiated from ES/iPS cells focusing on mitochondria

    2016.04
    -
    2020.03

    Grants-in-Aid for Scientific Research, Moritoh Satoru, Grant-in-Aid for Challenging Exploratory Research, No Setting

    　View Summary

    We developed a new differentiation protocol for retinal cells from mouse embryonic stem cells based on the previously reported methods of human pluripotent stem cells. After embryoid body formation, we plated embryoid bodies on the Matrigel-coated dishes and covered them using Matrigel-containing retinal differentiation medium. This protocol is relatively simple and easy. Although our first aim of this project was to purify the photoreceptors which have high mitochondrial content differentiated from ES/iPS cells as in the case of previous reports of the purification of the cardiomyocytes, we could not achieve the purification of mitochondria-rich photoreceptors.

  • シナプスの保護における分子基盤の探求

    2013.04
    -
    2015.03

    若手研究(B), Principal investigator

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