Analysis of craniosynostosis caused by mutations in fibroblast growth factor receptors and their related genes

成纤维细胞生长因子受体及其相关基因突变所致颅缝早闭分析

基本信息

  • 批准号:
    12671764
  • 负责人:
  • 金额:
    $ 2.11万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2000
  • 资助国家:
    日本
  • 起止时间:
    2000 至 2002
  • 项目状态:
    已结题

项目摘要

In order to understand the function of the genes involved in mammalian skull vault development we first investigated the possibility of adenoviral vector-mediated gene expression in vivo. Mouse fetal skull was injected enhanced green fluorescent protein (eGFP) expression vector subcutaneously by ex-utero surgery. There are four layers identified in the developing mouse skull, skin, connective tissue, osteogenic and meningeal layers. In the osteogenic layer each skull bone domain appears at the lateral side of the skull and grow expanding up to the top. Infection specificity in the layers varied according to the stage of the injection. The meningeal layer was preferably infected when the injection was carried out on embryonic day (E)13.5, the osteogenic layer was a major infection site when E14 fetuses were injected. The injection on E14.5 resulted in eGFP expression only in the connective tissue layer.A transcription factor, Twist, is known to function in maintenance of undifferentiated condition and expressed in undifferentiated mesenchymal cells of the osteogenic layer and ubiquitously in the meningeal layer during the prenatal skull development. We injected the Twist expression vector into either right or left side of a fetal skull. When the infection was achieved in the osteogenic layer bone domain patterning was not affected but the bone on injected side became slightly thinner than that of uninjected side. When Twist was over-expressed in the meningeal layer, however, growth of the bone domains of injected side was inhibited and they stayed at the lateral side of the skull. Expression levels of bone morphogenetic protein 4 and 7, which are normally expressed in the meningeal layer, were severely decreased in Twist over-expressed site. From these results we suggest that a signal from the meningeal layer promotes bone domain growth in the osteogenic layer.
为了了解哺乳动物颅顶发育相关基因的功能,我们首先研究腺病毒载体介导的基因在体内表达的可能性。将增强型绿色荧光蛋白(EGFP)表达载体经宫外皮下注射小鼠胎头骨。在发育中的小鼠颅骨、皮肤、结缔组织、成骨和脑膜层中发现了四层。在成骨层中,每个颅骨骨域出现在颅骨的外侧,并向上扩展到顶部。蛋鸡的感染特异性因注射阶段的不同而不同。胚胎13.5天注射时以脑膜层感染为主,胚胎14天注射时主要感染部位为成骨层。注射E14.5后,EGFP仅在结缔组织层表达。转录因子Twist在胎儿期颅骨发育过程中,在成骨层的未分化间充质细胞和脑膜层普遍表达,在维持未分化状态方面发挥作用。我们将Twist表达载体注射到胎儿头骨的右侧或左侧。当感染发生在成骨层时,骨域构型不受影响,但注射侧的骨较未注射侧稍变薄。然而,当Twist在脑膜层过表达时,注射侧骨域的生长受到抑制,它们停留在颅骨的外侧。在Twist过度表达部位,正常表达于脑膜层的骨形态发生蛋白4和7的表达水平显著降低。根据这些结果,我们认为来自脑膜层的信号促进了成骨层中骨域的生长。

项目成果

期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Morriss-Kay G.M., Iseki S. and Johnson D.: "Genetic control of the cell proliferation-differentiation balance in the developing skull vault : roles of fibroblast growth factor receptor signalling pathways. In : The Molecular Basis of Skeletogenesis (ed. J
Morriss-Kay G.M.、Iseki S. 和 Johnson D.:“发育中的颅骨穹窿中细胞增殖分化平衡的遗传控制:成纤维细胞生长因子受体信号通路的作用。见:骨骼发生的分子基础(J 编)
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    0
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Jiang X., Iseki S., Maxson R.E., Sucov H.M. and Morriss-Kay G.M.: "Tissue origins and interactions in the mammalian skull vault"Dev. Biol.. 241. 106-116 (2002)
Jiang X.,Iseki S.,Maxson R.E.,Sucov H.M.
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Johnson D.: "Expression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for Twist in suture initiation and biogenesis."Mechanisms of Development. 91・1-2. 341-345 (2000)
Johnson D.:“Twist 和 Fgfr1、-2 和 -3 在发育中的小鼠冠状缝中的表达模式表明 Twist 在缝线起始和生物发生中发挥着关键作用。”发育机制 91・1-2。 2000)
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    0
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Hjiantoniou E.: "DNazyme-mediated cleavage of Twist transcripts and increase in cellular apoptosis."Biochem.Biophys Res.Commun.. 300. 178-181 (2003)
Hjiantoniou E.:“DNAzyme 介导的 Twist 转录物裂解和细胞凋亡增加。”Biochem.Biophys Res.Commun.. 300. 178-181 (2003)
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    0
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Kubota K., Iseki S., Kuroda S., Oida S., limura T., Duarte W.R., Ohya K., Ishikawa I. and Kasugai S.: "Synergistic wffect of fibroblast growth factor 4 in ectopic bone formation induced by bone morphogenetic protein 2"Bone. 31. 465-471 (2002)
Kubota K.、Iseki S.、Kuroda S.、Oida S.、limura T.、Duarte W.R.、Ohya K.、Ishikawa I. 和 Kasugai S.:“成纤维细胞生长因子 4 在骨诱导的异位骨形成中的协同作用
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ISEKI Sachiko其他文献

ISEKI Sachiko的其他文献

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{{ truncateString('ISEKI Sachiko', 18)}}的其他基金

Application of biomaterials for regulation of osteoblast differentiation to craniosynostosis
生物材料调控成骨细胞分化在颅缝早闭中的应用
  • 批准号:
    16K15746
  • 财政年份:
    2016
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Involvement of sonic hedgehog signaling in secondary palate formation
声波刺猬信号参与次级腭形成
  • 批准号:
    20390510
  • 财政年份:
    2008
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Inhibitory regulation of osteogenesis in sutures of mammalian skull
哺乳动物颅骨缝合线成骨的抑制调节
  • 批准号:
    15390554
  • 财政年份:
    2003
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

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将创新的分子佐剂方法与新型腺病毒载体递送相结合以产生通用流感疫苗
  • 批准号:
    10519005
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Combining innovative molecular adjuvanting approaches with novel adenoviral vector delivery to generate a universal influenza vaccine
将创新的分子佐剂方法与新型腺病毒载体递送相结合以产生通用流感疫苗
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    10653245
  • 财政年份:
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Development and manufacture of an improved replication-deficient simian adenoviral vector to prevent COVID-19
开发和制造改进的复制缺陷猿腺病毒载体以预防 COVID-19
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    MC_PC_20018
  • 财政年份:
    2020
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    Intramural
Enhanced respiratory syncytial virus disease or protection from infection depends on the subtype used for adenoviral vector vaccination
增强呼吸道合胞病毒病或预防感染取决于腺病毒载体疫苗接种所用的亚型
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    2019
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Development of Helper Dependent Adenoviral Vector
辅助依赖性腺病毒载体的开发
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    479436-2015
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    2015
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    $ 2.11万
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    Experience Awards (previously Industrial Undergraduate Student Research Awards)
Development of Helper Dependent Adenoviral Vector
辅助依赖性腺病毒载体的开发
  • 批准号:
    476642-2014
  • 财政年份:
    2015
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    $ 2.11万
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    Experience Awards (previously Industrial Undergraduate Student Research Awards)
Development of Helper Dependent Adenoviral Vector
辅助依赖性腺病毒载体的开发
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    469508-2014
  • 财政年份:
    2014
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    $ 2.11万
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Development of Helper Dependent Adenoviral Vector
辅助依赖性腺病毒载体的开发
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    462097-2014
  • 财政年份:
    2014
  • 资助金额:
    $ 2.11万
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    Experience Awards (previously Industrial Undergraduate Student Research Awards)
Gene therapy for head and neck cancer using replication-selective adenoviral vector
使用复制选择性腺病毒载体治疗头颈癌
  • 批准号:
    25670717
  • 财政年份:
    2013
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    $ 2.11万
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    Grant-in-Aid for Challenging Exploratory Research
Anti-proliferative activity of Adenoviral vector expressing short hairpin RNA targeting G-Protein coupled receptor (GPR87) in urothelial carcinoma
表达靶向 G 蛋白偶联受体 (GPR87) 的短发夹 RNA 的腺病毒载体在尿路上皮癌中的抗增殖活性
  • 批准号:
    25462482
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    Grant-in-Aid for Scientific Research (C)
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