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標題: | BCAS2透過Delta-Notch訊息傳遞調控果蠅翅膀發育 BCAS2 regulates Drosophila wing development via Delta-Notch signaling |
作者: | Yi-Chen Hsieh 謝怡真 |
指導教授: | 陳小梨 |
關鍵字: | BCAS2,果蠅,Delta-Notch 訊息傳遞,發育, BCAS2,Drosophila,Delta-Notch signaling,development, |
出版年 : | 2012 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64721 |
全文授權: | 有償授權 |
顯示於系所單位: | 微生物學科所 |
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