| Project/Area Number |
16570177
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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 | The University of Tokushima |
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Principal Investigator |
OHUCHI Hideyo The University of Tokushima, Faculty of Engineering, Associate Professor, 工学部, 助教授 (00253229)
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| Co-Investigator(Kenkyū-buntansha) |
MITO Taro The University of Tokushima, Faculty of Engineering, Assistant Professor, 工学部, 助手 (80322254)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Fibroblast Growth Factor / FGF10 / Organogenesis / Developmental Engineering / Cis-regulatory elements / Knockout mice / 内耳 / トランスジェニックマウス |
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| Research Abstract |
The purpose for this study was to analyze cis-regulatory elements of the mouse Fgf10 gene and to elucidate the FGF10-transcriptional network during vertebrate organogenesis. This year we have further analyzed the upstream 6.6kb region of the Fgf10 gene and studied the roles of FGF10 in eyelid and tooth development. We have found dozens of binding sites for nuclear receptor family members in the Fgf10 genome though in silico analysis. We next examined the role of Fgf10 during mouse eyelid development, as the Fgf10 knockout mice exhibit eye-open at birth. We found that FGF10 has a dual role in proliferation and migration during the early and later stages of eyelid development, respectively. Through explant culture of Fgf10-null eyelid anlagen it was found that exogenous FGF10 could rescue the expression of activin bB and transforming growth factor a (Tgfa), known to be required for eyelid closure. We also observed that the exogenous FGF10 protein induced F-actin accumulation in the mutant eyelid anlagen. We further examined filopodia of the eyelid leading edge cells, finding the length of the filopodia was significantly reduced in the mutant. These results have verified that FGF10 promotes eyelid closure through activating activin and TGFa-EGFR signaling. On the other hand, we found that the expression of Fgf10 disappears in the transitional stage from crown formation to root of the developing tooth. We examined postnatal growth in the incisors of Fgf10-deficient mice after implantation under the kidney capsule, finding that the growth at the labial side in the mutant mice mimicked the development of limited-growth teeth. These and further results have suggested that the disappearance of Fgf10 signaling leads to the transition from crown to root formation. The functional studies elucidated here will facilitate the analysis and application of the Fgf10-regulatory elements for developmental and regenerative medicine in the future.
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