| Project/Area Number |
12670746
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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 | Shiga University Medical Science |
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Principal Investigator |
FUJINO Hidetoshi Shiga University Medical Science, Medicine, Assistant Professor, 医学部, 助手 (40209078)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Masao Shiga University Medical Science, Medicine, Associated Professor, 医学部, 講師 (40188909)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | PAX3 / Sox4 / bis-diamine / cardiac development / conotruncal septation / neural tube closure / neural crest cell / RT-RCP |
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| Research Abstract |
1. A single dose of bis-diamine was administered to pregnant ICR mice on 7.5 days of gestation and the expression of PAX3 m-RNA in the embryonic nervous system was examined using semi-quantitative RT-PCR method. The control embryos showed PAX3 expression in the central nervous system was first detected on 8.5 embryonic day (ED), reached the maximum level on 11.5 and diminished on 13.5 ED. The treated embryos demonstrated the same expressional pattern of the control embryos and no significant difference in the amount of m-RNA was seen between the control and treated embryos.
2. Expressions of transcriptional factors important for the development of the central nervous system were evaluated in the mice embryos treated with bis-diamine. Expression of EMX-1 was significantly reduced on 10.5 and 1 1.5 ED in the embryonic brain treated with bis-diamine, compared with that in control embryos. Expressional patterns of Wnt-3 and AP-2 were not affected by bis-diamine administration.
3. Sox4 is a Sry-box family of transcriptional factors and exclusively expressed in the conal ridge of the outflow tract and the atrioventricular canal of embryonic hearts. The gene disruption in mice causes abnormal development of the semilunar valves, resulting in cardiac anomalies such as infundibular ventricular septal defect and persistent truncus arteriosus. Sox4 expressions in the embryonic brain and heart were down-regulated by bis-diamine administration.
Expressional pattern of m-RNA shown in this study indicated that bis-diamine affected the development of the central nervous system and, subsequently, disturbed migration of neural crest cells into the heart. The contribution of PAX3 to the conotruncal septaion was not clear in this study. Sox4 may be involved in the migration of neural crest cells and the differentiation to the vascular smooth muscle cells.
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