| Co-Investigator(Kenkyū-buntansha) |
SAKANO Hitoshi Associate Professor, Department of Molecular and Cell Biology, University of Cal, バークレー校・分子細胞生物学部, 準教授
NAKAWA Fumikiyo Research Associate, Department of Cell Biology, National Institute for Basic Bio, 基礎生物学研究所, 助手 (10241233)
MOCHII Makoto Research Associate, Department of Developmental Biology, National Institute for, 基礎生物学研究所, 助手 (90202358)
KODAMA Ryuji Associate Professor, Department of Developmental Biology, National Institute for, 基礎生物学研究所, 助教授 (90161950)
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| Research Abstract |
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
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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
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