| Co-Investigator(Kenkyū-buntansha) |
JOYNER Alexandra L. NYU., Medical Center, Professor, メディカルセンター, 教授
REDDI A.Harr カリフォルニア大学デービス校, 医学部, 教授
HASHIGUCHI Isamu Kyshu Univ., Dentistry, Research Associate, 歯学部, 助手 (10150476)
HARRI Reddi A. UCDA., Medicine, Professor
REDDI A Hari カリフォルニア大学, デイビス校・医学部, 教授
赤峰 昭文 九州大学, 歯学部, 教授 (00117053)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Research Abstract |
We have cloned and characterized a new member of the BMP/TGFb superfamily, Gdf 11, from rat dental(incisor) pulp RNA by RT-PCR using degenerate primers. The mature carboxyl-terminal domain encoded by Gdf11 is 85% identical to mouse Growth/differentiation factor 8 (Gdf8). Northern blot analysis revealed Gdf11 is expressed in adult dental pulp and brain. In situ hybridization of sections and whole mount embryos demonstrated Gdf 11 is expressed as early as 8.5 days post coitus (dpc) in the tail bud. At 10.5 dpc, it is expressed in the branchial arches, limb bud, tail bud and posterior dorsal neural tube. Later, it is expressed in terminaliy differentiated odontoblasts, the nasal epithelium, retina and specific regions of the brain. These studies indicate that Gdf11 could cooperate with other BMP/TGFb superfamily members in multiple developmental processes. The mice lack of Gdf 11, however, did not have phenotype.
We have also cloned a new member of the zinc finger transcription factor, G23
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from incisor pulp RNA by RT-PCR using degenerate primers. The five zinc finger domain encoded by mouse G23 has almost 65 % amino acid sequence homology with Gli1, Gli2 and Gli3. Northern blot analysis revealed G23 is expressed in dental pulp, kidney and testis. In situ hybridization of sections and whole mount embryos demonstrated G23 is first detected diffusely in forelimb and hindlimb bud at 10.0 days post coitus (dpc). At 10.5 dpc, it is expressed in the branchial arches, limb bud, craniofacial border, and ventral part of the tail. Later, it is expressed in whisker follicle, intervertebral disc, kidney, and testis. The expression of G23 was compared with the genes involved in the Sonic Hedgehog (Shh) signaling pathway, Shh, Ptc, Gui1, Gli2, and Gli3 during tooth development. G23 was found to be expressed in dental papillae in temporally and spatially overlapped pattern with Ptc, Glil, Gli2, and Gli3 where Shh are not expressed. In order to assess the possible role of G23 in Shh signaling pathway and its interaction with Glis, the expression of G23 in Glil/Gli2 mutant and Shh mutant was examined during tooth development and kidney development. The G23 transcript was upregulated in tooth germ in Gli2-/- and Glil+/- ; Gli2-/- mutant, suggesting G23 might have a role of suppresser on the Shh signaling pathway during tooth development. The expression of G23 in kidney was not changed in Gli2-/- and Glil+/- ; Gli2-/- mutant. There might be different feedback pathways operating to regulate the action of Shh in the cell proliferation and maintenance between tooth and kidney development. G23 might have redundant function and display similar signaling activity with Gli members. To examine more directly the role of G23 in embryogenesis, special reference to tooth and kidney development, the targeted gene disruption of G23 in the mouse was performed. Less
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