| Budget Amount *help |
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Embryonic organogenesis proceeds under the strong influence of tissue interactions involving extracellular signaling molecules. The signaling molecules, once received by a cell, activate intracellular mechanisms which lead to dynamic changes in transcriptional regulation and to a new state of cell differentiation. Thus, transcriptional regulation is the basis of cell differentiation, while tissue interactions spatially and temporally organize the events of this occurrence.
Sox transcription factors, binding to ATTGTT and related sequences, are emerging as key players of cell differentiation, among which Sox2 is probably the best studied case. Sox2 is expressed in the ICM and epiblast before gastrulation, then the primordium of CNS, sensory placodes, anterior alimentary tract, etc.
In the case of lens induction, Sox2 expression is activated in the region of head ectoderm already expressing Pax6, and this initiates lens development. We demonstrate that Sox2 and Pax6 proteins physically interact and make a ternary complex with regulatory region DNAs, and the complex strongly activates genes for lens differentiation.
Generally, Sox2 activates genes only in cooperation with partner factors which bind to an adjacent site of a regulatory region, and it pairs with different partners in different type of cells. In this way, the same Sox2 protein regulates distinct sets of genes in cell type-dependent manner.
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