Gene Regulation in the Cell Commitment and Differentiation

细胞定型和分化中的基因调控

• 批准号: 03044150
• 负责人: EGUCHI Goro
• 金额: $ 5.76万
• 依托单位: National Institute for Basic Biology, Okazaki National Research Institutes.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03044150/
• 关键词: Cell differentiation; Determination of differentiation; Transdifferentiation; Multipotency; Regulatory gene; Pigmented epithelial cell; Central nervous system; Growth factor; レンズ細胞; 脱分化; 再分化; 分化の多能性; 細胞外基質; 再文化

Based on the findings established through studies from 1991 to 1992, we have analyzed the regulatory mechanisms of genes which are thought to be responsible for determination of differentiation in multipotent undifferentiated cells, using the system of lens transdifferentiation of pigmented epithelial cells (PECs) of older chick embryos. In addition, we have collaborated to find out the mechanism regulating development and differentiation of the central nervous system in mammals. The following results were obtained.PECs from older chick embryos can readily transdifferentiate to lens cells via multipotent dedifferentiated cells (dePECs) under the permissive condition. Two genes, designated as pP344 and pP64, were found to be required for stable maintenance of differentiated states and lens transdifferentiation of PECs. Analyses of structure and function of these two genes have revealed that the product of pP344 gene exhibited the activity as a protease inhibitor, was expressed specifica … More lly by the retinal PECs, and play an essential role to regulate the differentiated state through cooperative functions with extracellular matrix components of PECs themselves. The pP64 gene, which was found to encodes TGFbeta-binding proteins, produced 5.0kb and 6.0kb transcripts by alternative splicing of its mRNAs. The well-differentiated PECs express 5.0kb mRNAs as major product in addition to 6.0kb mRNAs. The protein produced by 5.0kb mRNAs is secreted by PECs in situ but that produced by 6.0kb mRNAs is trapped by the extracellular matrix of PECs. In addition, in the multipotent dePECs and transdifferentiated lens cells the pP344 is completely inactivated and 6.0kb product of the pP64 gene is only expressed. Moreover, bFGF and TGFbeta, which is produced by PECs, dePECs and also lens cells, were found to be responsible for regulation of the differentiated state of PECs.In addition to the finding to suggest the strong possibility of occurrence of gene rearrangement during development of the central nervous system in mice, the findings avobe described must provide the essential information required for the prospective studies to understand the molecular mechanism which rules determination of differentiation of multipotent undifferentiated cells during development. Less

在1991 - 1992年研究成果的基础上，我们利用鸡胚色素上皮细胞晶状体转分化系统，分析了多能未分化细胞中决定分化的基因的调控机制。此外，我们还合作发现了哺乳动物中枢神经系统发育和分化的调节机制。得到了以下结果：在允许条件下，大龄鸡胚的多能去分化细胞（depec）可以很容易地通过多能去分化细胞（depec）转分化为晶状体细胞。我们发现两个基因pP344和pP64是稳定维持PECs的分化状态和晶状体转分化所必需的。对这两个基因的结构和功能分析表明，pP344基因的产物具有蛋白酶抑制剂的活性，在视网膜PECs中特异表达，并通过与PECs自身的细胞外基质组分协同作用，在调节分化状态中发挥重要作用。pP64基因编码tgf - β结合蛋白，通过其mrna的选择性剪接产生5.0kb和6.0kb的转录本。除了表达6.0kb mrna外，分化良好的PECs主要表达5.0kb mrna。5.0kb mrna产生的蛋白被PECs原位分泌，而6.0kb mrna产生的蛋白被PECs的细胞外基质捕获。此外，在多能deecs和转分化晶状体细胞中，pP344完全失活，仅表达6.0kb的pP64基因产物。此外，发现由PECs、depec和晶状体细胞产生的bFGF和tgf β负责调节PECs的分化状态。除了提示在小鼠中枢神经系统发育过程中发生基因重排的可能性很大之外，本文所描述的发现必须为前瞻性研究提供必要的信息，以了解发育过程中多能未分化细胞分化决定的分子机制。少

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