Molecular basis of palate formation

腭形成的分子基础

• 批准号: 14370586
• 负责人: WANAKA Akio
• 金额: $ 8.96万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370586/
• 关键词: 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

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.

我们已经鉴定出LIM同源结构域基因家族的一个成员，命名为L3/Lhx8。该基因在发育中的胚胎的基底前脑和口腔间充质中特异表达。为了探索L3/Lhx8基因的功能，我们产生了L3ILhx8基因缺失的突变小鼠。这些小鼠患有腭裂，出生后不久就死亡了。这一现象促使我们进一步研究L3/Lhx8基因在腭部形成中的作用。我们比较了参与细胞间相互作用的各种基因在突变小鼠和野生型小鼠中的表达。我们发现，核心蛋白在突变的上颌骨中表达上调，而野生上颚则表现出正常的表达模式。核心蛋白聚糖被认为是转化生长因子β家族成员的诱饵受体，转化生长因子β3-KO小鼠出现了腭裂。我们假设L3/Lhx8参与了转化生长因子β信号通路。在外植体培养系统中，突变小鼠的味觉即使在相互接触时也不能融合。当培养液中加入转化生长因子β3时，以剂量依赖的方式挽救腭裂融合。我们认为，L3/Lhx8调节核心蛋白的表达，从而调节局部Igeβ家族成员的浓度。

项目成果

Hagino, S. et al.: "Slit and glypican-1 mRNAs are coexpressed in the reactive astrocytes of the injured adult brain"Glia. (in press). (2003)

Hagino, S. 等人：“Slit 和磷脂酰肌醇蛋白聚糖 1 mRNA 在受损成人大脑的反应性星形胶质细胞中共表达”神经胶质细胞。

Hikake, T., T.MOri, K.Iseki, S.Hagino, Y.Zhang, H.Takagi, S.Yokota, A.Wanaka: "Comparison of expression patterns between CREB family transcription factor OASIS and proteoglycan core protein genes during murine tooth development"Anat.Embryol.(Berl). 206. 3

Hikake, T., T.MOri, K.Iseki, S.Hagino, Y.Zhang, H.Takagi, S.Yokota, A.Wanaka：“CREB ​​家族转录因子 OASIS 和蛋白聚糖核心蛋白基因在

Hikake, T.et al.: "Comparison of expression patterns between CREB family transcription factor OASIS and proteoglycan core protein genes during murine tooth development."Anat.Embryol.(Berl). 206. 373-380 (2003)

Hikake, T.等人：“小鼠牙齿发育过程中 CREB ​​家族转录因子 OASIS 和蛋白多糖核心蛋白基因的表达模式比较。”Anat.Embryol.(Berl)。

Tetsuji Mori, zhang Yuxing, Hiromi Takaki, Mayumi Takeuchi, Ken Iseki, Seita Hagino, Junichi Kitanaka, Motohiko takemura, Hidemi Misawa, Masahito Ikawa, Masaru Okabe, Akio Wanaka: "The LIM homeobox gene, L3/Lhx8, is necessary for proper development of bas

Tetsuji Mori、zhang Yuxing、Hiromi Takaki、Mayumi Takeuchi、Ken Iseki、Seita Hagino、Junichi Kitanaka、Motohiko takemura、Hidemi Misawa、Masahito Ikawa、Masaru Okabe、Akio Wanaka：“LIM 同源盒基因 L3/Lhx8 对于正确的表达是必需的。

Shibaguchi, T., J.Kato, M.Abe, Y.tamamura, M.J.Tabata, J.G.Liu, M.Iwamoto, S.wakisaka, A.Wanaka, K.Kurisu: "Expression and role of Lhx8 in murine tooth development"Arch.Histol.Cytol.. 66. 95-108 (2003)

Shibaguchi, T., J.Kato, M.Abe, Y.tamamura, M.J.Tabata, J.G.Liu, M.Iwamoto, S.wakisaka, A.Wanaka, K.Kurisu：“Lhx8 在小鼠牙齿发育中的表达和作用”