| Project/Area Number |
11234201
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKATSUJI Norio Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (80237312)
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| Co-Investigator(Kenkyū-buntansha) |
NOCE Toshiaki Mitsubishi-kagaku Institute of Life Science, Senior Scientist, 主任研究員
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥153,000,000 (Direct Cost: ¥153,000,000)
Fiscal Year 2002: ¥37,400,000 (Direct Cost: ¥37,400,000)
Fiscal Year 2001: ¥37,500,000 (Direct Cost: ¥37,500,000)
Fiscal Year 2000: ¥38,100,000 (Direct Cost: ¥38,100,000)
Fiscal Year 1999: ¥40,000,000 (Direct Cost: ¥40,000,000)
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| Keywords | Primordial germ cells / tudor gene / vasa gene / spermatogenesis / germ cell development / meiosis / germ plasm / nuage / 性分化 / 精巣 / Vasa遺伝子 |
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| Research Abstract |
Mouse primordial germ cells (PGCs) migrate from the base of allantois to the genital ridge. They proliferate during the migration and after the arrival until initiation of the sex-differentiation of fetal gonads. Then, PGCS enter into the prophase of the first meiotic division in the ovary to become oocytes, while those in the testis become mitotically arrested to become prospermatogonia. Relatively little was known : about differentiation of PGCs into oocytes or prospermatogonia in fetal gonads. Observation of ectopic germ cells and studies of cultured PGCs have indicated that both male and female PGCs show cell-autonomous entry into meiosis and differentiation into oocytes if they were not in the fetal testis.
We showed that both female and male PGCs isolated from the fetal gonads immediately after their arrival, or those isolated from the mesenteries at 9.5-10.5 dpc during their migration, entered into the leptotene stage of the first meiotic division after dissociation and cultivati
… More
on for a few days on feeder cells, thus showing that meiotic competence is already acquired by PGCs before reaching the fetal gonads. We also demonstrated that the LIF/gp130-mediated signal suppressed the meiotic transition by PGCs in vitro.
Apoptosis is another remarkable event in the fetal germ cells. We investigated regulation of the germ cell apoptosis by using a mouse strain in which bcl-x gene was disrupted. Analysis of heterozygotic embryos and mice revealed that prospermatogonia are more prone to apoptosis than oocytes. Such differences appeared at the beginning of sex-differentiation of germ cells.
We also investigated the mouse tudor-related gene, mtr-1, in mouse male germ cells. It is expressed in the prospermatogonia in fetal testis and more abundantly in spermatocytes in adult testes. In mice, nuage structures called chromatoid bodies appear during postnatal spermatogenesis rather than during germ-line specification. Previously, a mouse homologue of vasa, one of the Drosophila polar granule components, has been identified. Its product was present in chromatoid bodies, and the targeted disruption of the gene showed defects in postnatal spermatogenesis. TUDOR is another component of polar granules in Drosophila, and it contains ten repeated copies of the tudor domain. We have identified a novel mtr-1 gene that encodes four repeated copies of the tudor domain. Mtr-1 expression was restricted to germ-line cells, and the transcript was most abundant in spermatocytes in the adult testis. The MTR-1 protein was present predominantly in spermatocytes and round spermatids, showing granular distribution in the cytoplasm. These granules co-localized precisely with those of cytoplasmic ribonucleoproteins, and they were present exclusively in both the inter-mitochondrial nuages and perinuclear chromatoid bodies. Less
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