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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Kai-Li Su | en |
| dc.contributor.author | 蘇凱立 | zh_TW |
| dc.date.accessioned | 2021-06-15T05:14:35Z | - |
| dc.date.available | 2016-09-21 | |
| dc.date.copyright | 2011-09-21 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-17 | |
| dc.identifier.citation | References
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(2009). Cell adhesion in amphibian gastrulation. International review of cell and molecular biology 278, 215-275. Wong, H.C., Bourdelas, A., Krauss, A., Lee, H.J., Shao, Y., Wu, D., Mlodzik, M., Shi, D.L., and Zheng, J. (2003). Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled. Molecular cell 12, 1251-1260. Wu, Y.C., Cheng, T.W., Lee, M.C., and Weng, N.Y. (2002). Distinct rac activation pathways control Caenorhabditis elegans cell migration and axon outgrowth. Developmental biology 250, 145-155. Wu, Y.C., and Horvitz, H.R. (1998). C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392, 501-504. Wu, Y.C., Tsai, M.C., Cheng, L.C., Chou, C.J., and Weng, N.Y. (2001). C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment. Developmental cell 1, 491-502. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46541 | - |
| dc.description.abstract | 細胞遷移在多細胞生物發育的過程中扮演著重要的角色。雌雄同體線蟲中兩條性腺的發育是由位於性腺前端的兩顆遠頂細胞在特定的發育時期進行遷移所形成的。這兩顆遠頂細胞依時間順序在幼蟲時期會進行三個階段的遷移，分別稱為遠離生殖孔、腹側到背側、接近生殖孔，最終形成兩條對稱的U型性腺臂。先前的研究揭示有一群細胞外的引導因子會調控遠頂細胞的遷移。同時，屬於引導因子之ㄧ的Netrin家族蛋白UNC-6與其接受器UNC-5與UNC-40已經被詳細研究會影響遠頂細胞從腹側移動到背側的過程。此外，先前我們實驗室發現一個屬於Frizzled家族的訊息接受器MOM-5突變後會產生發生於幼蟲第四期的遠頂細胞向心遷移的缺陷，同時亦發現在線蟲中五種Wnt (LIN-44，EGL-20，CWN-1，CWN-2與MOM-2)突變後也會產生與MOM-5突變株相同的突變表徵，並證實CED-5/GEF與CED-10/Rac參予MOM-5訊息傳遞路徑且作用在DSH-1的下游。這顯示MOM-5作為接受器接收來自引導因子Wnt的訊息且傳遞至下游DSH-1調控遠頂細胞的遷移。然而對於這些引導因子如何傳遞入細胞導致細胞骨架的改變進而造成細胞的移動目前仍不清楚。藉由分析dsh-1的ok1445 allele我們發現其中一種DSH-1的isoform, dsh-1b會影響遠頂細胞向心的移動。此外，dsh-1(ok1445)的突變性狀可經由表現dsh-1b被拯救，這個結果顯示dsh-1b參與遠頂細胞向心的遷移。我們同時也發現在酵母菌雙雜交實驗中DSH-1b可結合CED-5，顯示DSH-1b蛋白可直接與CED-5蛋白結合。整合先前實驗室的研究，我們提供ㄧ個模型，MOM-5可接受特定的Wnt並傳遞訊息給下游的DSH-1，DSH-1藉由與CED-5結合活化CED-10促進遠頂細胞向心的遷移。 | zh_TW |
| dc.description.abstract | Cell migration is essential for the development of multicelluar animals. The gonad formation in the hermaphrodite of Caenorhabditis elegans is guided by stag-specific migration of two leader cells, distal tip cells (DTCs), which are located at the leading edge of each gonad arm. DTCs undergo three sequential phases of linear migration –centrifugal, circumferential and centripetal during larval stages and lead the formation of symmetrical U-shaped gonad arms. Previous studies have shown that a set of conserved extracellular guidance cues control the migration of DTCs. It is well studied that the circumferential migration of DTC is mediated in part by the guidance molecule netrin UNC-6 and its receptors UNC-5 and UNC-4. Our laboratory has previously discovered that mom-5 mutants exhibit a centripetal migration defect in late L4 stage and double mutants of Wnt family member (lin-44;egl-20 and cwn-1;cwn-2) also show the centripetal migration defect. Besides, CED-5/Dock180 and CED-10/Rac which are reported as engulfing genes before are downstream of DSH-1 and involved in MOM-5 pathway. It seems that MOM-5 serves as a guidance receptor receiving guidance signal from Wnts to the downstream components DSH-1 to promote DTC migration. However, it remains unclear how these extracellular cue are transduced by the cell into the cytoskeletal and molecular motor activities that result in cell migration. Analyzing the ok1445 allele of dsh-1 mutant, we demonstrate that loss of the function of dsh-1b which is one of the three isoforms in dsh-1 gene results in DTC centripetal migration defect. The defect of dsh-1(ok1445) could be rescued by expression of DSH-1b under the dsh-1b endogenous promoter. Therefore, dsh-1b is required for correct migration in DTC centripetal migration. Furthermore, I demonstrated that DSH-1b is able to bind to CED-5/Dock180 in the yeast two-hybrid assay. This finding suggests that DSH-1b may signal to CED-5/Dock180 directly. Combine previous works in our lab, we show that MOM-5/Frizzled acts with specific Wnts and tranduces signal to DSH-1b which recruit CED-5/Dock180-CED-12/ELMO complex through direct interaction with CED-5/Dock180 for CED-10/Rac activation to promote DTC centripetal migration. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T05:14:35Z (GMT). No. of bitstreams: 1 ntu-100-R98b43028-1.pdf: 991032 bytes, checksum: 8993af05bdb255cfe6e75869b600ee78 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Table of Contents
致謝…………………………………………………………………………………………………Ⅰ 中文摘要…………………………………………………………………………………………Ⅱ 英文摘要…………………………………………………………………………………………..Ⅲ Table of Contents…………………………………………………………………………………Ⅴ Introduction…………………………………………………………………………………………1 Cell migration is important in development and maintenance of multicellular organism………...1 Distal tip cell as a simple model to study the spatiotemperal control of cell migration in C. Elegans…………………………………………………………………………………………….2 Genetic analysis of DTC migration in each phase in hermaphrodite worms……………………...4 1. Centrifugal migration phase…………………………………………………………………...4 2. Circumferential migration phase………………………………………………………………5 3. Centripetal migration phase……………………………………………………………………6 Materials and Methods……………………………………………………………………………10 Strains and Genetics……………………………………………………………………………...10 Transgenic worms………………………………………………………………………………...10 Molecular and biology……………………………………………………………………………10 Yeast two-hybrid analysis……………………………………………….………………………..11 Heat shock experiment…………………………………………………………………………...13 Analysis of phenotypes…………………………………………………………………………...14 Results……………………………………………………………………………………………..15 MOM-5 can not transduce Wnt signal by direct bonding CED-2/5/12 ternary complex or CED-10/Rac……………………………………………………………………………………...15 DSH-1b interacts with CED-5/Dock180 in the yeast two-hybrid assay…………………………17 LIN-44 might be an instructive signal to attract anterior and posterior DTC……………………19 EGL-20 might be a permissive signal for posterior DTC centripetal migration…………………21 Discussion…………………………………………………………………………………………..23 References………………………………………………………………………………………….26 Figures and Tables…………………………………………………………………………………34 Figure1. Schematic diagram show the direction and path of the three sequential phase of DTC migration…………………………………………………………………………………………34 Figure2. DTC centripetal migration defect in mom-5, ced-5 and lin-44;egl-20 mutants……….35 Figure3. Frizzled family protein structure and C-terminal cytosolic region analysis…………..36 Figure4. MOM-5 intracellular domain can not direct bind to CED-2, CED-5, CED-10 or CED-12…………………………………………………………………………………………...37 Figure5. The dsh-1 gene structure……………………………………………………………….38 Figure6. DSH-1b physically interacts with CED-5 in vitro……………………………………..39 Table1. dsh-1b rescues the DTC centriprtal migration defect in the dsh-1(ok1445) mutants……40 Table2. Ectopic expression of LIN-44…………………………………………………………...41 Table3. Ectopic expression of EGL-20…………………………………………………………42 Table S1. Potential genes regulate MOM-5 expression at L4 stage…………………………….43 | |
| dc.language.iso | en | |
| dc.subject | 向心遷移 | zh_TW |
| dc.subject | 遠頂細胞 | zh_TW |
| dc.subject | 性腺臂 | zh_TW |
| dc.subject | Distal tip cell | en |
| dc.subject | gonad arm | en |
| dc.subject | centripetal migration | en |
| dc.title | 線蟲LIN-44/Wnt與DSH-1b/Dishevelled參與在遠頂細胞遷移角色的探討 | zh_TW |
| dc.title | The role of Caenorhabditis elegans LIN-44/Wnt and DSH-1/Dishevelled in distal tip cell migration | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 潘俊良(Chun-Liang Pan),廖秀娟(Hsiu-Chuan Liao) | |
| dc.subject.keyword | 遠頂細胞,性腺臂,向心遷移, | zh_TW |
| dc.subject.keyword | Distal tip cell,gonad arm,centripetal migration, | en |
| dc.relation.page | 43 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-18 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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