| Project/Area Number |
18570210
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
KISHIMOTO Yasuyuki National Institute of Genetics, Department of Developmental Genetics, Assistant Professor (90370113)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | vertebrate / maternal fector / early embryogenesis / molybdenum cofactor / FGF / sulfate / zebrafish / bobtail |
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| Research Abstract |
Maternal factors are synthesized during oogenesis, and control early events of animal embryogenesis. However, in vertebrates, little is known about molecular mechanisms by which maternal factors regulate early developmental processes. We report here characterization of a zebrafish maternal-effect mutation, bobtail (btl). Embryos produced from the btl homozygous mothers exhibited defects in morphogenesis of the midbrain-hindbrain boundary and posterior mesodermal patterning. We found that implantation of Fgf8-soaked beads did not induce ERK phosphorylation in the btl mutant embryos, suggesting that Fgf signaling is impaired in the btl mutant embryos. We performed positional cloning and identified that a gene encoding molybdenum cofactor synthesis step-1 (MOCS1) was mutated in the btl mutant. MOCS1 is involved in molybdenum cofactor (MoCo) biosynthesis and catalyzes conversion of GTP into cyclic pyranopterin monophosphate (cPMP). We discovered that the btl mutant phenotypes were rescued by injection of cPMP, indicating that the product of MOCS1 is essential for Fgf signaling. Sulfite oxidase is a known MoCo-dependent enzyme that catalyzes conversion of sulfite into sulfate. We further discovered that the btl mutant phenotypes were rescued by treatment with inorganic sulfate, suggesting that a sulfite oxidase deficiency is the cause of the observed btl phenotypes. Our present study demonstrated that production of MoCo, thereby synthesis of sulfate, is essential for Fgf signaling during vertebrate embryonic development.
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