| Project/Area Number |
13120201
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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 | Research Institute, Osaka Medical Center for Maternal and Child Health |
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Principal Investigator |
MATSU Yasuhisai Research Institute, Osaka Medical Center for Maternal and Child Health, Department of Embryology, Director of the department, 病院病態部門, 部長 (40241575)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥25,600,000 (Direct Cost: ¥25,600,000)
Fiscal Year 2002: ¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2001: ¥12,800,000 (Direct Cost: ¥12,800,000)
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| Keywords | primordial germ cell / epiblast / mil-1 / BMP4 / Smad5 / genomic imprinting / Igf2r / サブトラクション / mil-1 / mil-2 / インターフェロン誘導性遺伝子 / RAN binding protein / インプリンティング / メチル化 / bisulfate法 |
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| Research Abstract |
To study molecular mechanisms regulating mouse primordial germ cell (PGC) formation from pluripotential epiblast cells, we first attempted to isolate genes potentially involved in the process of PGC formation. We identified candidate genes, mil-1 and mil-2, belonging to the interferon induced transmembrane protein gene family from isolated PGCs, that were referentially expressed in forming PGCs. From their expression patterns and their structural features, it was suggested that those genes were involved in cell-cell interaction regulating PGC determination. We also found that BMP4 expressed in extraembryonic ectoderm induced the PGC precursors within the adjacent proximal epiblat in a primary culture in which PGCs differentiated form epiblast. In addition, extraembryonic ectoderm first induced SmadS, an intracellular signaling molecule for BMP4, in proximal epiblast before BMP4 induced the precursors, and this led proximal epiblast cells to acquire responsiveness to BMP4. We next studied the erasure of methylation imprinting that specifically occurred in differentiating PGC to understand mechanisms of PGC differentiation. We found that demethyaltion of a typical genomic imprinting gene, Igf2r was initiated in migrating PGCs, and that the demethylation rapidly progressed when PGCs colonized genital ridges. These observations suggested that the erasure of methylation imprinting was regulated by environment of genital ridges independent- and dependent mechanisms.
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