Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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Research Abstract |
In chicken embryo, the definitive endoderm which gives rise to the epithelial lining of the digestive tract is established during gastrulation from epiblast. At the beginning, endoderm forms as an unspecified simple flat-sheet structure, and gradually becomes regionalized into antero-posteriorly and dorso-ventrally divided organs during embryogenesis. Finally, endodermal epithelium in each organ exhibits unique morphologies and gene expression patterns to perform its specific physiological functions. It is reported that the endoderm is necessary for the specification of other tissues such as forebrain, heart and inner ear. Therefore, to understand the detailed mechanisms of the endodermal specification is very helpful in clarifying the whole body plan in vertebrates. However, little is known about mechanisms underlying the initial steps of the regional differentiation (regionalization) in the endoderm. In this thesis I investigated to elucidate the timing of regionalization of endoderm, and molecular mechanisms essential for the early regionalization in endoderm. This study clarified the precise timing of specification in foregut and hindgut endoderm, and based on these results, revealed the expression profile of many novel genes which may be important for the initial regionalization in endoderm. Moreover, the results I obtained that the signaling modifier of BMPs, sizzled, plays an essential role for regionalization of foregut, especially in liver development, illuminate importance of modification of the gradient of secreted molecules in specification of complex morphogenesis. The study presented here must provide a framework for further elucidation of molecular mechanisms underlying the differentiation along the body axis at early stage development not only in endoderm, but also whole body of the vertebrate.
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