| Project/Area Number |
10044271
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SHIOTA Kohei Kyoto Univ. Grad. Sch. Med., Professor, 医学研究科, 教授 (80109529)
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| Co-Investigator(Kenkyū-buntansha) |
HATAYAMA Takumi Kyoto Parmaceut. College, Professor, 教授 (10094484)
MIURA Takashi Kyoto Univ. Grad. Sch. Med., Res. Associte, 医学研究科, 特別研究員
NARUSE Ichiro Kyoto Univ. Grad. Sch. Med., Assoc. Prof., 医学研究科, 助教授 (20113326)
李 忠連 大阪医科大学, 講師 (80319532)
滝川 俊也 京都大学, 医学研究科, 助手 (90263095)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Physical agents / Hyperthermia / Developmental abnormalities / Embryos / Hox genes / Central nervous system / Neurulation / Folic acid / 熱ショック / 胎児脳 / ニューロン / 脊柱 / トランスフォーメーション / 形態形成 / 脳発生異常 / 遺伝子発現 / 熱ショック蛋白 / 先天異常 |
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| Research Abstract |
Exposure of developing embryos to such physical agents as irradiation and hyperthermia can cause various developmental abnormalities, and the central nervous system and axial skeleton of the embryo are most susceptible to their teratogenic effects. In the present study, we examined the neurulation process in human embryos and carried out a series of experiments using mice, and obtained the following results.
1. In human embryos, in addition to the future cervical region that is widely accepted as an initiation site of neural tube (NT) closure, NT closure initiates also at the mesencephalic-rhombencephalic boundary and at the rostral end of the neural groove. The caudal extension of the first closure initiating at the cervical level was found to proceed down to the caudal end of the neural groove where the posterior neuropre is formed. This new finding of the human NT closure can explain the pathogenesis of various types of neural tube defects (NTD).
2. When pregnant mice were heat-stressed at 42 or 43 C at gestational day (GD) 13-14, the proliferation and migration of neural precursor cells were significantly suppressed and apoptotic neuronal death increased in the embryonic brain.
3. Heat stress at GD14-16 inhibited the migration of neurons to the primordial facial ganglia and retarded the ganglion formation in mouse embryos.
4. Heat stress at GD7-9 caused stage-specific shifts of Hox gene expression in the embryos and produced corresponding homeotic vertebral transformations.
5. When pregnant mice were given folic acid (FA) (3 mg/kg) daily from GD0 through GD9 and heated at GD8, the prevalence of NTD in the fetuses was significantly reduced.
The above results showed that exposure of embryos to hyperthermia at the critical period of organogenesis can interfere with gene expression, resulting in a variety of developmental abnormalities, and that FA supplementation early in pregnancy can suppress heat-induced teratogenesis.
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