Project/Area Number |
14370586
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Morphological basic dentistry
|
Research Institution | Nara Medical University |
Principal Investigator |
WANAKA Akio Nara Medical University, Anatomy, Professor, 医学部, 教授 (90210989)
|
Co-Investigator(Kenkyū-buntansha) |
TATSUMI Kouko Nara Medical University, Anatomy, Research Associate, 医学部, 助手 (90208033)
HAGA Satomi Nara Medical University, Anatomy, Assistant Professor, 医学部, 講師 (20192263)
|
Project Period (FY) |
2002 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
|
Keywords | Cleft palate / Mutant mice / LIM-homeodomain gene / TGF beta / Decorin / Explant culture / 上皮-間葉相互作用 / 器官培養 / TGFΒ |
Research Abstract |
We have identified a member of LIM-homeodomain gene family, designated as L3/Lhx8. This gene is specifically expressed in the basal forebrain and oral mesenchyme of the developing embryo. To explore functions of the L3/Lhx8, we generated mutant mice that were deficient of the L3ILhx8, gene. These mice suffered from cleft palate and died shortly after birth. This phenomenon prompted us to further examine roles of L3/Lhx8 gene on palate formation. We compared expressions of various genes that were involved in cell-cell interactions in the mutant and wild-type mice. We found that decorin was upregulated in mutant palate shelves, while wild palate showed normal expression patterns. Decorin is known to behave as a decoy receptor for TGF beta family members and TGF beta3-KO mice exhibited cleft palate. We hypothesized that L3/Lhx8 is involved in TGF beta signaling pathway. In explant culture system, palates from mutant mice did not fuse even when they were contacted with each other. When TGF beta3 was added in the culture medium, palatal fusion was rescued in a dose-dependent manner. We concluded that L3/Lhx8 regulates decorin expression and thereby modulates local concentration of IGE beta family member.
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