The molecular basis of the functional retinal circuitry

• Project/Area Number: 24687010
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Animal physiology/Animal behavior
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Onishi Akishi 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 研究員 (70569102)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥27,560,000 (Direct Cost: ¥21,200,000、Indirect Cost: ¥6,360,000); Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2012: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
• Keywords: 網膜 / 視細胞 / 中心窩 / 神経回路 / 視覚 / 神経回路形成

Outline of Final Research Achievements

In this study, we performed functional screening of molecules that govern specific synaptic connection between photoreceptors (rod, S cone and M cone) and secondary neurons (horizontal cell and bipolar cells) in the mouse retina. When we electroporated Susd3 cDNA, a single transmembrane protein specifically expressed in rod photoreceptors in the mouse retinas, the photoreceptors showed branching synaptic terminals that targeted secondary neurons in a dose dependent manner. Next, we developed double knockout mice of Aldh1a1 and Cyp1b1, enzymes that synthesize ligands for Rxrg, and observed significant decrease of M cones. In addition, Aldh1a1 deficient mice showed choroidal hypoplasia.

Research Products

• [Journal Article] Optimized Culture System to Induce Neurite Outgrowth From Retinal Ganglion Cells in Three-Dimensional Retinal Aggregates Differentiated From Mouse and Human Embryonic Stem Cells. (2016)
  • Author(s): Maekawa Y, Onishi A, Matsushita K, Koide N, Mandai M, Suzuma K, Kitaoka T, Kuwahara A, Ozone C, Nakano T, Eiraku M, Takahashi M
  • Journal Title: Curr Eye Res Volume: 19 Pages: 1-11
  • DOI: 10.3109/02713683.2015.1038359
  • Peer Reviewed / Open Access
• [Journal Article] G9a histone methyltransferase activity in retinal progenitors is essential for proper differentiation and survival of mouse retinal cells (2012)
  • Author(s): Katoh K, Yamazaki R, Onishi A, Sanuki R, Furukawa T
  • Journal Title: J Neurosci Volume: 32(49) Issue: 49 Pages: 17658-70
  • DOI: 10.1523/jneurosci.1869-12.2012
  • Peer Reviewed
• [Presentation] Neural retina-derived retinoic acids control choroidal vascular development (2016)
  • Author(s): Goto S, Onishi A, Ito H, Sakaguchi H, Nishida K, Takahashi M
  • Organizer: Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: アメリカ合衆国 シアトル
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] Culture of retinal ganglion cells (RGC) purified from 3D retinal organoids differentiated from human induced pluripotent stem (iPS) cells (2016)
  • Author(s): Kobayashi W, Onishi A, Takihara Y, Inatani M, Nakazawa T, Takahashi M
  • Organizer: Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: アメリカ合衆国 シアトル
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] Extracellular matrices preferable to neurite outgrowth from retinal organoids differentiated from mouse embryonic stem cells (2016)
  • Author(s): Maekawa Y, Onishi A, Koide N, Suzuma K, Mandai M, Kitaoka T, Takahashi M
  • Organizer: Extracellular matrices preferable to neurite outgrowth from retinal organoids differentiated from mouse embryonic stem cells
  • Place of Presentation: アメリカ合衆国 シアトル
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] マウスiPS細胞より分化した3次元網膜におけるサプリメントの視細胞保護効果の検討 (2016)
  • Author(s): 伊藤晋一郎、大西暁士、髙橋政代、児玉徹也、角谷俊文
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-04-07
• [Presentation] 神経網膜由来のレチノイン酸による脈絡膜発達制御機構 (2016)
  • Author(s): 後藤聡、大西暁士、伊藤裕美、坂口裕和、西田幸二、高橋政代
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-04-07
• [Presentation] マウス及びヒト胚性幹細胞からの3次元分化培養網膜を用いた網膜神経節細胞からの神経突起伸長 (2015)
  • Author(s): 前川有紀、大西暁士、松下恵三、小出直史、万代道子、鈴間潔、桑原篤、大曽根親文、中野徳重、永楽元次、北岡隆、高橋政代
  • Organizer: 日本組織細胞化学学会
  • Place of Presentation: 関西医科大学
  • Year and Date: 2015-10-03
• [Presentation] Neurite outgrowth from retinal ganglion cells in self-organizing mouse and human retinal tissues differentiated from embryonic stem cells (2015)
  • Author(s): Maekawa Y, Onishi A, Matsushita K, Koide N, Mandai M, Suzuma K, Kitaoka T, Kuwahara A, Ozone C, Nakano T, Eiraku M, Takahashi M.
  • Organizer: The International Society for Stem Cell Research
  • Place of Presentation: スウェーデン ストックホルム
  • Year and Date: 2015-06-24
  • Int'l Joint Research
• [Presentation] Chemically induced photoreceptor degeneration in 3D retinal aggregates from mouse iPS cells (2015)
  • Author(s): Ito M, Onishi A, Iraha S, Takahashi M.
  • Organizer: The International Society for Stem Cell Research
  • Place of Presentation: スウェーデン ストックホルム
  • Year and Date: 2015-06-24
  • Int'l Joint Research