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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳小梨 | |
| dc.contributor.author | Yi-Chen Hsieh | en |
| dc.contributor.author | 謝怡真 | zh_TW |
| dc.date.accessioned | 2021-06-16T22:58:02Z | - |
| dc.date.available | 2014-09-19 | |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-09 | |
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SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly. Nucleic Acids Res 33, 6868-83. Grote, M., Wolf, E., Will, C. L., Lemm, I., Agafonov, D. E., Schomburg, A., Fischle, W., Urlaub, H. and Luhrmann, R. (2010). Molecular architecture of the human Prp19/CDC5L complex. Mol Cell Biol 30, 2105-19. Haenlin, M., Kramatschek, B. and Campos-Ortega, J. A. (1990). The pattern of transcription of the neurogenic gene Delta of Drosophila melanogaster. Development 110, 905-14. Hay, B. A., Maile, R. and Rubin, G. M. (1997). P element insertion-dependent gene activation in the Drosophila eye. Proc Natl Acad Sci U S A 94, 5195-200. Huppert, S. S., Jacobsen, T. L. and Muskavitch, M. A. (1997). Feedback regulation is central to Delta-Notch signalling required for Drosophila wing vein morphogenesis. Development 124, 3283-91. Jack, J., Dorsett, D., Delotto, Y. and Liu, S. (1991). 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The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate. Development 124, 1485-95. Monaghan, J., Xu, F., Gao, M., Zhao, Q., Palma, K., Long, C., Chen, S., Zhang, Y. and Li, X. (2009). Two Prp19-like U-box proteins in the MOS4-associated complex play redundant roles in plant innate immunity. PLoS Pathog 5, e1000526. Nagaraj, R. and Banerjee, U. (2007). Combinatorial signaling in the specification of primary pigment cells in the Drosophila eye. Development 134, 825-31. Nagasaki, K., Maass, N., Manabe, T., Hanzawa, H., Tsukada, T., Kikuchi, K. and Yamaguchi, K. (1999). Identification of a novel gene, DAM1, amplified at chromosome 1p13.3-21 region in human breast cancer cell lines. Cancer Lett 140, 219-26. Neubauer, G., King, A., Rappsilber, J., Calvio, C., Watson, M., Ajuh, P., Sleeman, J., Lamond, A. and Mann, M. (1998). 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The cyclin L homolog MOS12 and the MOS4-associated complex are required for the proper splicing of plant resistance genes. Plant J 70, 916-28. Zecca, M. and Struhl, G. (2007). Recruitment of cells into the Drosophila wing primordium by a feed-forward circuit of vestigial autoregulation. Development 134, 3001-10. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64721 | - |
| dc.description.abstract | BCAS2 (Breast carcinoma amplified sequence 2)是一個核蛋白，也是抑癌蛋白p53的負調控者，過去的研究中發現BCAS2除了透過p53，還可能藉由其他方式調控細胞生長。我們實驗室的研究亦指出BCAS2的確是參與核醣核酸剪切體 hPrp19/CDC5L complex的核心成員之一，並且參與核醣核酸的剪切。我們也發現當果蠅體內BCAS2相似蛋白(dBCAS2)的表現在全身被降低時，會造成果蠅無法發育為成蟲；而利用組織特異性啟動子在果蠅翅膀降低dBCAS2的表現，則會造成翅膀的殘缺，這些證據顯示BCAS2在發育過程中的重要性。另外，在dBCAS2被默化的果蠅翅膀中異位表現人類的BCAS2 (hBCAS2)可以挽救翅膀殘缺的情形，這顯示人類與果蠅的BCAS2扮演相似的角色。
在本篇論文研究中，我們利用組織特異性啟動子engrailed-GAL4表現dBCAS2雙鏈RNA，默化果蠅翅膀中的dBCAS2，尋找受dBCAS2調控的訊息傳遞路徑。透過Delta-Notch訊息傳遞路徑下游基因cut與E(spl)m8表現量的改變，我們發現Delta-Notch訊息傳遞路徑的活性會因為dBCAS2表現量減少而下降。當dBCAS2被默化時，會降低 delta基因在轉譯的過程中核醣核酸剪切的效率，進而導致Delta表現量下降、影響Delta-Notch 訊息的傳遞。在大量表現Delta的果蠅眼睛中將dBCAS2默化，可以挽救Delta在眼睛中過量表現時所產生的異常結果，更加證明dBCAS2會調控Delta的表現。在果蠅體內大量表現hBCAS2或是dBCAS2不會產生任何異常現象，但若在dBCAS2被默化的果蠅翅膀中大量表現hBCAS2或是dBCAS2，都可以挽救Delta-Notch訊息傳遞路徑活性降低時的異常現象。藉由這些研究結果，我們認為dBCAS2可能透過調控Delta-Notch訊息傳遞路徑而參與在果蠅翅膀發育的過程當中。 | zh_TW |
| dc.description.abstract | Previously, we found that breast carcinoma amplified sequence 2 (BCAS2), a nuclear protein and a p53 negative regulator, is involved in cell growth regulations. Then, we proved that BCAS2 is indeed a component of hPrp19/CDC5L complex and functions in pre-mRNA splicing. Ubiquitous silencing of dBCAS2 in the whole body and tissue-specific knockdown of dBCAS2 in the wings result in larval lethality and wing deformity respectively, suggesting the importance of dBCAS2 in fly development. Additionally, ectopic expression of hBCAS2 in dBCAS2-depleted fly can rescue the lethality and wing deformity, indicating that hBCAS2 plays a similar role to dBCAS2. In this study, we found that dBCAS2 regulates the activity of Delta-Notch signaling. Deprivation of dBCAS2 down-regulates the expression of Delta ligand by impeding splicing efficiency of delta, and hence diminishing the transcription of Delta-Notch signaling target genes, such as cut and E(spl)m8. Furthermore, depletion of dBCAS2 and ectopic expression of either hBCAS2 or dBCAS2, which exhibits normal phenotypes, can rescue aberrant Delta-overexpressing retinas and abnormal dBCAS2-depleted wing discs respectively, providing supportive evidence for the regulation of Delta-Notch signaling by dBCAS2. Our results indicate that dBCAS2 participates in the regulation of Delta-Notch signaling in Drosophila wing development. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T22:58:02Z (GMT). No. of bitstreams: 1 ntu-101-R99445109-1.pdf: 2590589 bytes, checksum: a1c66b5f0bdeb397cb8c1bcae947c062 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 論文口試委員審定書 i
致謝 ii 中文摘要 iii ABSTRACT iv CHAPTER 1 INTRODUCTION 1 1.1 The basic knowledge of BCAS2 1 1.2 The conservation of BCAS2 across species 2 1.3 The crucial roles of members in Prp19-associated splicing complex in embryonic development 3 1.4 The canonical Delta-Notch signaling pathway 4 1.5 Delta-Notch signaling in Drosophila eye and wing development 5 1.6 Delta-Notch signaling regulates cell differentiation and tissue development. 6 1.7 Specific aims 7 CHAPTER 2 MATERIALS AND METHODS 8 2.1 Fly genetics and fly stocks 8 2.2 Immunostaining 9 2.3 Quantitative RT-PCR analysis 10 2.4 Construction of dBCAS2 transgenic fly 14 2.6 Adult wing images and fluorescent images processing and analysis 18 CHAPTER 3 RESULTS 19 3.1 BCAS2 is evolutionary conserved and is an essential protein in development. 19 3.2 dBCAS2 is involved in the regulation of Delta-Notch signaling. 19 3.3 Depletion of dBCAS2 down-regulates the expression of Delta and Notch. 22 3.4 Silencing of dBCAS2 down-regulates the expression of Delta through the process of pre-mRNA splicing. 23 3.5 Human BCAS2 can rescue the malfunction of Delta-Notch signaling resulted from the deprivation of dBCAS2. 25 3.6 Ectopic expression of hBCAS2 does not alter the expression of Delta and Notch and the activity of Delta-Notch signaling. 26 3.7 Overexpression of dBCAS2 does not affect wing development, the activity of Delta-Notch signaling and the level of Delta and Notch. 26 3.8 3xFLAG-dBCAS2 can restore the effects caused by the deprivation of dBCAS2 27 3.9 Depletion of dBCAS2 can rescue the aberrant eye resulted from overexpression of wild-type Delta. 28 CHAPTER 4 DISCUSSION 31 REFERENCES 38 FIGURES 43 APPENDIX 67 | |
| dc.language.iso | en | |
| dc.title | BCAS2透過Delta-Notch訊息傳遞調控果蠅翅膀發育 | zh_TW |
| dc.title | BCAS2 regulates Drosophila wing development via Delta-Notch signaling | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳君泰,詹世鵬,譚婉玉 | |
| dc.subject.keyword | BCAS2,果蠅,Delta-Notch 訊息傳遞,發育, | zh_TW |
| dc.subject.keyword | BCAS2,Drosophila,Delta-Notch signaling,development, | en |
| dc.relation.page | 67 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-09 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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