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研究生:李函儒
研究生(外文):Han-Ru Li
論文名稱:研究PRL在海膽胚胎發育中的功能
論文名稱(外文):The role of PRL during sea urchin development
指導教授:蘇怡璇蘇怡璇引用關係
指導教授(外文):Yi-Hsien Su
學位類別:碩士
校院名稱:國立臺灣海洋大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:97
中文關鍵詞:海膽胚胎發育肝再生去磷酸酶初級間質細胞次級間質細胞骨頭生成色素細胞
外文關鍵詞:sea urchinembryo developmentphosphatase or regenerating liverprimary mesenchyme cellsecondary mesenchyme cellskeletogenesispigment cell
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人類Phosphatase of regenerating liver (PRL)家族包含PRL-1、PRL-2、PRL-3,此去磷酸酶家族被認為與致癌有關。PRL在腫瘤的生成及發育中扮演重要的角色,如癌細胞侵襲、細胞遷移、血管新生和癌細胞轉移,然而PRL在胚胎發育中扮演的角色仍不清楚。海膽胚胎因構造簡單且方便觀察,因此成為研究細胞行為及型態的模式生物。過去的研究發現抑制海膽胚胎的去磷酸酶會影響endomesoderm的形成,包含骨針的發育。本論文將探討SpPRL在海膽胚胎發育中的功能。海膽基因體中只有一個PRL基因,其會轉譯出174個胺基酸並且與人類PRLs的相似度很高。SpPRL為母體表現基因,在胚胎發育期會廣泛的分布,蛋白質在囊胚期後會集中表現於secondary mesenchyme cell (SMC)。弱化SpPRL的表現或抑制其酵素活性皆會影響海膽胚胎的骨針發育,並形成不正常型態的色素細胞。在SpPRL表現被抑制的胚胎中,許多與骨針形成細胞primary mesenchyme cell (PMC)特化及分化相關的基因表現量都降低。因此猜測SpPRL經由調控PMC與SMC之間的關係影響骨針發育。
The phosphatase of regenerating liver (PRL) family, consisting of PRL-1, PRL-2, and PRL-3 in human, represents a group of phosphatases related to tumorigenesis. PRL family plays critical roles in the processes of tumor initiation and development, such as cancer cell invasion, migration, angiogenesis, and metastasis. However, the role of PRL during development is unclear. Sea urchin embryos have been a research model for studying cell behaviors and morphogenesis because of its simple organization that are easily observed. Blocking the expression of several phosphatases in the sea urchin embryo has been shown to interfere with the formation of endomesoderm including skeletogenesis. In this study, I identified sea urchin PRL and studied its function during embryogenesis. Sea urchin contains a single PRL gene (SpPRL) that encodes for a 174-aa protein with high similarity to its human homologs. SpPRL is expressed maternally and ubiquitously during development, and proteins are localized dominantly in secondary mesenchyme cells (SMCs) after the mesenchyme blastula stage. In SpPRL-knockdown and hPRL-3 inhibitor-treated embryos, the formation of the embryonic skeleton was affected and the morphology of pigment cells was abnormal. The expression levels of several primary mesenchyme cell (PMC, skeletogenic lineage cells) differentiation and specification genes were declined in SpPRL knockdown embryos. Therefore, I proposed that SpPRL affects skeletogenesis through interactions between SMCs and PMCs.
中文摘要 i
英文摘要 ii
目錄 iii

第一章、緒論 1
一、PRLs家族介紹 1
二、海膽模式生物 2
三、內中胚層基因調控網路 (Endomesoderm gene regulatory network) 3
四、海膽胚胎之骨針發育 (Skeletogenesis) 5
五、Secondary mesenchyme cell的分化 7
六、實驗動機 8

第二章、實驗材料與方法 9

第三章、實驗結果 33
一、PRL基因序列在海膽與其他物種間很保守 33
二、SpPRL基因在不同海膽胚胎時期皆有表現 33
三、SpPRL蛋白質在mesenchyme blastula時期後位於SMC前驅細胞與由SMC分化的pigment cell和blastocoelar cell 34
四、弱化SpPRL表現影響海膽胚胎骨針發育 35
五、弱化SpPRL表現會影響骨針生長但對腸子發育無明顯影響 36
六、弱化SpPRL表現導致PMC下游標示基因表現下降 37
七、弱化SpPRL表現影響pigment cell分化 39
八、抑制SpPRL活性影響胚胎骨針發育 41
九、抑制SpPRL活性造成pigment cell數目減少且分化受影響 43
十、不同時期抑制SpPRL活性均會影響骨針與pigment cell發育 45
十一、SpPRL基因過度表現影響胚胎骨針生長 46
十二、SpPRL過度表現對PMC和SMC標示基因之影響 47

第四章、討論 49
一、SpPRL mRNA與蛋白質表現位置不一致 49
二、推測SpPRL不是透過ingression 與外胚層影響骨針發育 49
三、抑制SpPRL表現使多數的PMC基因表現也受影響 51
四、Prenylation motif對SpPRL功能的執行扮演重要的角色 52
五、推測SpPRL活性會影響pigment cell分化與細胞分裂 53
六、總結 53

第五章、文獻參考 55
附圖 60
附錄 78
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