2013 Fiscal Year Final Research Report
Molecular mechanism underlying sexual development of male germ cells
| Project/Area Number |
21227008
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Developmental biology
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
SAGA Yumiko 国立遺伝学研究所, 系統生物研究センター, 教授 (50221271)
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| Co-Investigator(Kenkyū-buntansha) |
KOKUBO Hiroki 国立遺伝学研究所, 系統生物研究センター, 助教 (10270480)
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| Co-Investigator(Renkei-kenkyūsha) |
SUZUKI Atsushi 横浜国立大学, 工学研究院, 准教授 (60467058)
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| Project Period (FY) |
2009-05-11 – 2014-03-31
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| Keywords | 生殖細胞 / RNA結合タンパク質 / 性分化 / 精子幹細胞 / ＣＮＯＴ複合体 |
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| Research Abstract |
In mouse germ cell development, the activation of an RNA binding protein Nanos2 is a critical step for male germ cell differentiation. We found that TGF-b signal (nodal/activin) mediated by Smad2 signaling is required for the Nanos2 induction. Once Nanos2 is induced, it localizes to P-bodies and interacts with CNOT complex, by which target RNAs are degraded. Nanos2 suppresses female pathway and promotes male pathway by repressing RNAs involved in the maintenance of PGCs, meiosis and mitosis in embryonic gonads. Nanos2 is also expressed in spermatogonial stem cells and plays an important role for the maintenance of stem cells. In the absence of Nanos2, stem cells can not maintain the stem cell property and quickly differentiate. We found that coordination of stem cells between self-renewal and differentiation is regulated by both extrinsic niche signals such as GDNF, FGF, RA and stem cell intrinsic factors such as Nanos2.
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