Molecular mechanisms of tinman induction by Dpp in the dorsal mesoderm of Drosophila.
Item
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Title
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Molecular mechanisms of tinman induction by Dpp in the dorsal mesoderm of Drosophila.
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Identifier
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AAI9917715
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identifier
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9917715
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Creator
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Xu, Xiaolei.
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Contributor
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Adviser: Manfred Frasch
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Genetics
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Abstract
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decapentaplegic (dpp) is a transforming growth factor-beta (TGF-beta) homologue in Drosophila, which plays essential roles as an inductive molecule in diverse steps of cell fate determination. During gastrulation, Dpp is secreted from the dorsal ectoderm and induces the formation of dorsal mesoderm, which later develops into visceral mesoderm, dorsal muscles and heart. The restriction of the expression of tinman, a NK homeobox gene, from the whole mesoderm to the dorsal mesoderm reflects this inductive event. In this study, tin-D, a 349bp Dpp-responsive element from the tinman enhancer, was identified and dissected to address the molecular mechanisms underlying this inductive process. A 32bp sub-element D3 was defined as a minimal Dpp-responsive element that is able to drive gene expression in dorsal areas of the embryo. The tissue-specific induction in the dorsal mesoderm requires the presence of another sub-element, D1, which specifically binds Tinman protein. D1 mediates a mesoderm-specific activity that consists of tinman autoregulation and acts in concert with the inductive signals. Additional observations suggested that a repressor can bind to D1 and prevent tin-D activity in the Dpp signaling tissue, i.e., the dorsal ectoderm. The minimal Dpp-responsive element D3 was used to isolate binding factors through yeast one hybrid screening, which resulted in the cloning of Medea, the common-mediator Smad of Drosophila. A variety of in vitro and in vivo experiments showed that Medea mediates the dorsal inductive signal of Dpp by directly binding to several GC-rich motifs in the tin-D element, including the D3 sub-element. The transduction of the Dpp signal to the tinman promoter may additionally require a CAATGT binding transcription factor. The potential functions of other factors in this pathway that were identified in the yeast one hybrid screens, including HMG-D, ccf-B, DEAF-1 and Adf-1, are also discussed. A comprehensive model combining the synergistic and antagonistic interactions is proposed to explain the molecular mechanisms of both the establishment of the dorsal-ventral polarity in Drosophila mesoderm and the signal transduction of TGF-beta at the transcriptional level.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
