Underlying mechanism of germline sex determination by FOXL3 and its co-factors
| Project/Area Number |
19K23749
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0702:Biology at cellular to organismal levels, and related fields
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 生殖細胞 / 性決定 / 卵形成 / メダカ / FOXL3 / FBXO47 / コヒーシン / 減数分裂の性差 / foxl3 / 性 / IP-MS |
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| Outline of Research at the Start |
生殖細胞の性決定（卵になるか精子になるかの運命決定）のスイッチ因子としてメダカで同定された転写因子FOXL3は、その下流でゲノム高次構造の性的二型を構築し、性特異的な遺伝子発現を制御している可能性が示唆されている。本研究では、免疫沈降-質量分析法を用いてFOXL3の共因子を網羅的に探索し、FOXL3が生殖細胞の性を司る分子メカニズムを解明することを目的としている。
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| Outline of Final Research Achievements |
Using CRISPR/Cas9 system, I generated medaka mutant lines of fbxo47 and rec8a, direct targets of FOXL3. fbxo47-mutant females were sterile, while males were fertile. The mutant ovaries lacked follicles, and chromosome in germ cells exhibited ring-like morphology possibly caused by telomere fusion. Furthermore, the fbxo47-mutant germ cells committed into spermatogenesis, suggesting that FBXO47 has a role in suppression of spermatogenesis. rec8a-mutant females were also sterile, and progression of meiosis was severely defected in germ cells. These results firstly revealed the molecular pathways that initiates several events in female germ cells (e.g. folliculogenesis, suppression of spermatogenesis, and meiosis progression).
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| Academic Significance and Societal Importance of the Research Achievements |
REC8AとFBXO47はそれぞれ染色体の高次構造とタンパク質分解に関わる因子であり、これらの事象と生殖細胞の性決定との関連が本研究で初めて示された。今後REC8AとFBXO47の機能を詳細に調べることで、生殖細胞の性を決める仕組みと卵を作り出す仕組みが分子レベルでより詳細に明らかになると考えられる。
そして卵や精子への経路を決める仕組みが明らかになれば、畜産・水産業において家畜や養殖魚の繁殖効率上昇や、生殖医療技術の改善につながると期待される。
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] foxl3, a sexual switch in germ cells, initiates two independent molecular pathways for commitment to oogenesis in medaka.2020
Author(s)
Kikuchi, M., Nishimura, T., Ishishita, S., Matsuda, Y. and Tanaka, M. (in press)
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 117
Issue: 22
Pages: 12174-12181
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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