2007 Fiscal Year Final Research Report Summary
Molecular Genetics of Holoprosencephaly
| Project/Area Number |
18591177
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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 |
Pediatrics
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| Research Institution | Kitasato University (2007)
National Research Institute for Child Health and Development (2006) |
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Principal Investigator |
MIYASHITA Toshiyuki Kitasato University, School of Medicine, Dept. of Molecular Genetics, Professor (60174182)
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| Co-Investigator(Kenkyū-buntansha) |
FIKII Katsunori Chiba University, Graduate School of Medicine, Dept. of Pediatrics, Research Associate (70344992)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Genetics / Holoprosencephaly / Cerebral Development / Polymorphism |
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| Research Abstract |
Holoprosencephaly (HPE) is a congenital disorder in which the formation of cerebral hemisphere is inhibited to a various degree. We found a patient with middle interhemispheric variant (also called syntelencephaly), a subtype of HPE, carrying a deletion in the long arm of chromosome 6. Using a high-resolution oligonucleotide microarray, we showed that the deletion is about 10 Mb-long including a promoter, exon 1 and exon 2 of the EYA4 gene. This result prompted us to investigate the function of the EYA4 protein.
The luciferase assay using a Gli-luciferase reporter revealed that EYA4 promotes sonic hedgehog (SHH) pathway in cooperation with SIX3, a product of one of the HPE responsible genes. Moreover, EYA4 colocalized with SIX3 in the nucleus when tagged proteins were transiently expressed in HeLa cells and these two proteins were coimmunoprecipitated with each other. These results indicate that EYA4 promotes SHH pathway directly or indirectly by associating with SIX3 and, therefore, is one of the candidate genes for HPE.
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