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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.author | Yu-Yun Chang | en |
| dc.contributor.author | 張玉雲 | zh_TW |
| dc.date.accessioned | 2021-07-01T08:12:36Z | - |
| dc.date.available | 2021-07-01T08:12:36Z | - |
| dc.date.issued | 2002 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75305 | - |
| dc.description.abstract | 在果蠅翅碟中，Hedgehog（Hh）在翅碟後端細胞合成，經由膽固醇和棕櫚酸的修飾後，被分泌到細胞膜上。Dispatched（Disp）為一個在Hh分泌細胞上的膜蛋白，具有SSD區域（sterol-sensing domain）可以幫助釋放嵌在細胞膜上的Hh蛋白質。在前端Hh接收細胞中，Tout-velu (Ttv)所合成的heparan sulfate proteoglycans (HSPGs)則可以促進Hh蛋白質在這些細胞間的傳遞。 rotini (rti)基因經由P-element所造成的突變株中顯現出其功能。此P-element插入一個轉錄複合體中，此複合體包含兩個在5'UTR互相重疊的註釋基因，CG7085和CG15387。由CG7085所合成的假定Rti為一個高基氏體蛋白質，廣泛地分佈在胚胎和翅碟中。Rti蛋白質的表現量影響了它的突變性狀。在rtiGLC胚胎中表現出絕對的母源效應產生扭曲及齒毛癒合（lawn-of-denticles）的突變性狀。我們確定rti會影響Hh在翅碟中的生成和訊息傳遞。在野生型翅碟中，約有5?6顆的前端細胞會表現Hh的標的基因Patched（Ptc）。當rti突變發生在Hh接收細胞時，僅有2?3顆細胞能表現Ptc。此Hh訊息減損的現象，與ttv突變的性狀相似但並非完全相同。特別地，rti突變會減少Hh生成細胞中Hh蛋白質的表現量。rti為目前所知第一個會影響Hh生成細胞中Hh表現量的基因。 除了對Hh生成及其訊息傳遞的影響外，rti也影響了HSPGs的表現量。rti對HSPGs影響的性狀相似於負責HSPGs聚合的ttv和負責HSPGs去乙醯化及硫酸化的sulfateless (sfl)所展現的性狀。rti，ttv和sfl這三個基因表現出未被發表過的相似性狀，即分別在Hh接收細胞和生成細胞中減少Ptc和Hh的表現量。我們認為ttv所影響的HSPGs並非只有幫助Hh蛋白質在Hh接收細胞間傳遞的功能。 由本論文的研究顯示，HSPGs和Hh之間具有交互作用，並且HSPGs可以維持Hh的有效濃度。因此我們推論HSPGs藉由和Hh的接合以達成對Hh蛋白質的保護，以拮抗其他分子對Hh所造成的分解作用。 | zh_TW |
| dc.description.abstract | In Drosophila wing disc, Hh is produced by posterior compartment cells where Hh is translated, modified by cholesterol and paltomitate, and secreted to the cell membrane afterward. Dispatched (Disp), a SSD-containing transmembrane protein, on the membrane of these secreting cells, helps the releasing of Hh from the cell membrane. In anterior compartment cells, the capability of Hh being transported across the Hh receiving cells is promoted by heparan sulfate proteoglycans (HSPGs) synthesized by tout-velu (ttv). The rotini (rti) gene function is manifested by P-element insertion mutations in a transcripts complex composed by two annotated genes, CG7085 and CG15387, which transcribe complementally with an overlapping region in 5'UTRs. The putative Rti is a Golgi protein encoded by CG7085 and expresses ubiquitously in embryo and wing disc. The quantity of Rti protein influences its mutational phenotypes. rti GLC embryos displayed strict maternal effect phenotype with twisted and lawn-of-denticles phenotype. Rti is confirmed its role in Hh production and signaling in wing disc. When rti mutant is in Hh receiving cells, only two to three cells expressing Patched (Ptc), one of the Hh target genes, comparing to the five Ptc-expressing cells in wild type. This Hh signaling defect is similar, but not the same, to that displayed in ttv mutant. More surprising, rti mutant reduces the expression of Hh in Hh producing cells. rti is the first gene known to affect Hh expression in producing cells till now. Besides its effects in Hh production and signaling, rti also affects HSPGs expression, the same phenotype displayed by ttv, a gene for polymerization of HSPGs, and sulfateless (sfl), which encodes an N-deacetylase/N-sulfotransferase. As the results were not reported previously, these three genes, rti, ttv and sfl, show the similar reduced Ptc expression in Hh receiving cells and the reduction of Hh protein in Hh producing cells. HSPGs do not simply assist the transportation of Hh as demonstrated by previously ttv study. From the study of this thesis, it suggests that HSPGs can interact with Hh and maintain its effective protein concentration. We propose that HSPGs protect Hh by binding to Hh and antagonize its degradation executed by other molecules on cell surface. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-01T08:12:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2002 | en |
| dc.description.tableofcontents | Introduction…………………………………………………………………………………………………………1 The Hedgehog signal transduction pathway……………………………………………………………………1 The production, secretion and reception of Hedgehog……………………………………………………2 The synthesis of heparan sulfate proteoglycans……………………………………………………………3 Chain initiation……………………………………………………………………………………………………4 Chain polymerization………………………………………………………………………………………………5 Polymer modification………………………………………………………………………………………………5 The biological function of heparan sulfate proteoglycan………………………………………………6 Genes involved in HSPGs synthesis in Drosophila…………………………………………………………7 (1) division abnormally delayed and dally-like……………………………………………………………8 (2) perlecan and syndecan………………………………………………………………………………………9 (3) sugarless and sulfateless…………………………………………………………………………………9 (4) tout-velu, DEXT2 and DEXT3………………………………………………………………………………10 (5) fringe connection……………………………………………………………………………………………11 (6) Sulfated………………………………………………………………………………………………………12 (7) pipe……………………………………………………………………………………………………………12 (8) Notum……………………………………………………………………………………………………………13 rotini, a novel segment polarity gene, affects Hh production and Ptc expression………………14 The relationship between HSPGs and Hh signaling…………………………………………………………15 Materials and Methods……………………………………………………………………………………………17 Fly stocks and maintenance……………………………………………………………………………………17 The autosomal FLP-DFS technique………………………………………………………………………………17 Heat shock treatment……………………………………………………………………………………………18 GAL4-UAS system……………………………………………………………………………………………………18 Antibody preparation……………………………………………………………………………………………18 Generation of recombinant clones in somatic tissues……………………………………………………19 Immunohistochemistry……………………………………………………………………………………………20 (a) Fluorescence imaginal discs antibody staining………………………………………………………20 Fixation and blocking……………………………………………………………………………………………20 Primary antibody…………………………………………………………………………………………………20 Secondary antibody………………………………………………………………………………………………21 Heparinase III treatment………………………………………………………………………………………21 (b) Fluorescence embryo antibody staining…………………………………………………………………21 Immunoblotting……………………………………………………………………………………………………22 Membrane Stripping………………………………………………………………………………………………22 Results………………………………………………………………………………………………………………24 P1164A4 mutation affects the putative CG7085 protein, Rti……………………………………………24 Rti expresses ubiquitously in embryo and wing disc……………………………………………………25 Rti is a putative Golgi protein………………………………………………………………………………26 The expression of Rti decreases in rti1164A4 mutant clones in wing and eye disc………………27 rti2170 affects Rti protein without giving any GLC phenotype………………………………………27 rti is a new gene affects HSPGs expression………………………………………………………………28 Both rti and ttv behave similarly and affect Hh, Ptc and HSPGs expression pattern……………30 sgl mutation does not affect 3G10, Ptc and Hh staining pattern……………………………………31 frc mutation has no effect on 3G10, Ptc and Hh expression……………………………………………32 sfl mutation causes reduced Ptc and Hh expression but not the 3G10 staining……………………33 Discussion…………………………………………………………………………………………………………35 rti1164A4 and rti2170 alleles…………………………………………………………………………………35 Rti is a putative Golgi protein………………………………………………………………………………37 The function of Rti………………………………………………………………………………………………39 HSPGs interact with Hh…………………………………………………………………………………………41 The possible mechanism of the interaction between HSPGs and Hh……………………………………42 The same or the different HSPGs……………………………………………………………………………45 HSPGs have non-autonomous effect……………………………………………………………………………47 Future prospects…………………………………………………………………………………………………48 Acknowledgement……………………………………………………………………………………………………50 References…………………………………………………………………………………………………………51 | |
| dc.language.iso | zh-TW | |
| dc.title | Heparan sulfate proteoglycans調節果蠅翅碟中Hedgehog蛋白質的穩定度 | zh_TW |
| dc.title | Heparan sulfate proteoglycans modulate Hedgehog maintenance in Drosophila wing discs | en |
| dc.date.schoolyear | 90-2 | |
| dc.description.degree | 碩士 | |
| dc.relation.page | 61 | |
| dc.rights.note | 未授權 | |
| dc.contributor.author-dept | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 動物學研究所 | zh_TW |
| 顯示於系所單位： | 動物學研究所 | |
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