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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李士傑(Shyh-Jye Lee) | |
| dc.contributor.author | Yi-Ching Liu | en |
| dc.contributor.author | 劉怡青 | zh_TW |
| dc.date.accessioned | 2021-06-15T05:55:33Z | - |
| dc.date.available | 2015-08-20 | |
| dc.date.copyright | 2010-08-20 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-17 | |
| dc.identifier.citation | Ali, I. U., Schriml, L. M., Dean, M., 1999. Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity. J Natl Cancer Inst. 91, 1922-32.
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Dev Biol. 164, 420-9. Thisse, C., Thisse, B., Schilling, T. F., Postlethwait, J. H., 1993. Structure of the Zebrafish Snail1 Gene and Its Expression in Wild-Type, Spadetail and No Tail Mutant Embryos. Development. 119, 1203-1215. Ueno, S., Kono, R., Iwao, Y., 2006. PTEN is required for the normal progression of gastrulation by repressing cell proliferation after MBT in Xenopus embryos. Dev Biol. 297, 274-83. Warga, R. M., Kimmel, C. B., 1990. Cell movements during epiboly and gastrulation in zebrafish. Development. 108, 569-80. Weinberg, E. S., Allende, M. L., Kelly, C. S., Abdelhamid, A., Murakami, T., Andermann, P., Doerre, O. G., Grunwald, D. J., Riggleman, B., 1996. Developmental regulation of zebrafish MyoD in wild-type, no tail and spadetail embryos. Development. 122, 271-80. Yeh, C.-M., Effects of PTENB on cell migration in gastrulating zebrafish embryos. Institute of Zoology, College of Life Science, Vol. Master. National Taiwan University, Taipei, Taiwan, 2008, pp. 37. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47337 | - |
| dc.description.abstract | 方向性細胞遷移是胚胎發育原腸腔時期形成三個主要胚層的主因。目前在斑馬魚關於此時期的研究所知，此種細胞遷移是藉由PI3 kinase磷酸化PIP2為PIP3所調控。Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)，是扮演與PI3 kinase相反作用的酵素，其主要作用是將PIP3上D3位置的磷酸根移除而成為PIP2。依此推測，Pten也可能在方向性細胞遷移的過程當中有所參與。因此我利用斑馬魚來探討抑制Pten的表現對於原腸腔時期細胞遷移有何影響。Pten在斑馬魚中有兩種同功異構物Ptena以及Ptenb，我運用ptenb的morpholino (MO)抑制了ptenb的表現之後發現細胞的方向性遷移受到了影響；此外雖然胚胎的形成並未受影響，然而其型態上的發育卻有所缺陷。而我們實驗室先前的實驗也利用PI3 kinase的抑制物，LY294002，削弱PI3 kinase的表現發現可以減弱Ptenb缺失所造成的缺陷，證實Ptenb對於細胞方向性遷移是藉由調控PIP2/PIP3之間的平衡而得之結果。進一步地，在ptenb受抑制的胚胎當中，位於側面具有聚合行為的細胞群其細胞極性也受到影響，同時觀察到肌動蛋白 (actin) 聚合程度有增加的趨勢。此外，我也發現，運用Cdc42的顯性負面(dominant-negative)分子T17NCdc42能夠抑制ptenb缺失所造成之缺陷。若是大量表現持續激活性之另一下游分子AKT1則可觀察到與ptenb 受抑制時同樣之現象，因此我認為此極性上的缺陷是來自於肌動蛋白聚合程度改變所影響而造成的結果。總體而言，Ptenb藉由調控PIP2/PIP3之間的平衡進一步調控了下游分子Cdc42以及Akt1進而調控肌動蛋白之聚合程度而影響了斑馬魚原腸腔時期的方向性細胞遷移。 | zh_TW |
| dc.description.abstract | During gastrulation, directional cell movements occur in the formation of three germ layers. Directional cell movements are known to be controlled by PI3 kinase by phosphorylating PIP2 to form PIP3 in zebrafish embryos. Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a counter enzyme of PI3 kinase by removing a phosphate group from PIP3. It is logical to hypothesize that Pten may also be involved in gastrulation cell migration. Here, I tested this hypothesis by investigating the effect of Pten knockdown on directed cell migration during gastrulation. I demonstrated that Ptenb, one of the Pten isoforms, regulates convergence and extension in zebrafish gastrulation by using the anti-sense morpholino oligo (MO). The effects of ptenb knockdown were through their control of PIP2/PIP3 balance, because previously in our lab showed that the Pten MO-induced defects could be rescued by PI3-kinase inhibitor, LY294002 and the knockdown of ptenb disturbed polarity and persistency of lateral convergent cells that was presumably via its regulation of actin dynamics, for the reason of actin polymerization was increased in the ptenb morphants. The downstream effectors, Akt1 and small GTPase Cdc42 would increase their activities in ptenb knockdown morphants; therefore, dominant negative Cdc42 was used and found to rescue the ptenb morphant. In addition, over-expression of human constitutively active akt1 mRNA showed similar convergent extension defects. In summary, I demonstrate here Ptenb by modulating PIP2/PIP3 signaling mediates directional cell migration by Akt1 and small GTPase to regulate actin polymerization during gastrulation in zebrafish. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T05:55:33Z (GMT). No. of bitstreams: 1 ntu-99-R97b41012-1.pdf: 1343726 bytes, checksum: dac8d766a51b476b6a896b0f2797feb5 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 iii Abstract v Contents 1 Introduction 3 Materials and Methods 7 Zebrafish maintenance and embryo collection 7 Morpholino oligonucleotide microinjections 7 Cloning and preparing mRNA 8 Whole-mount in situ hybridization (WISH) 10 Measurement and counting of embryos 11 DIC and confocal time-lapse cell migration recording 12 Cell transplantation 13 ptenb-/- zebrafish screening 13 Statistical analysis 14 Results 15 Sequencing, syntenic, and structural analysis of zebrafish ptenb 15 Knockdown of zebrafish ptenb affects convergence and extension 16 Zebrafish ptenb function is required non cell-autonomously for gastrulation cell migration 19 T17NCdc42 rescues ptenb morphant convergence and extension defects 21 Over-expression of human constitutively active AKT1 shows convergence and extension defects 22 PIP3 distribution analysis in gastrulating embryos 23 ptenb tMO1 causes convergence and extension defects on ptenb-/- embryos 24 Discussion 26 Ptenb regulates convergence and extension during gastrulation 27 Zebrafish Ptenb regulates gastrulation in coordination with PI3 kinase. 29 Zebrafish Ptenb regulates protrusive activities of lateral mesendodermal cells but not prechordal plate cells during gastrulation. 29 Zebrafish Ptenb controls convergence and extension during gastrulation via controlling actin polymerization and downstream Akt1 and small GTPases. 31 ptenb-/- embryos shows convergence and extension defects by ptenb tMO1 32 References 34 Figures 42 Figure 1. Sequence analysis of the zebrafish ptenb gene. 43 致謝 i 中文摘要 iii Abstract v Contents 1 Introduction 3 Materials and Methods 7 Zebrafish maintenance and embryo collection 7 Morpholino oligonucleotide microinjections 7 Cloning and preparing mRNA 8 Whole-mount in situ hybridization (WISH) 10 Measurement and counting of embryos 11 DIC and confocal time-lapse cell migration recording 12 Cell transplantation 13 ptenb-/- zebrafish screening 13 Statistical analysis 14 Results 15 Sequencing, syntenic, and structural analysis of zebrafish ptenb 15 Knockdown of zebrafish ptenb affects convergence and extension 16 Zebrafish ptenb function is required non cell-autonomously for gastrulation cell migration 19 T17NCdc42 rescues ptenb morphant convergence and extension defects 21 Over-expression of human constitutively active AKT1 shows convergence and extension defects 22 PIP3 distribution analysis in gastrulating embryos 23 ptenb tMO1 causes convergence and extension defects on ptenb-/- embryos 24 Discussion 26 Ptenb regulates convergence and extension during gastrulation 27 Zebrafish Ptenb regulates gastrulation in coordination with PI3 kinase. 29 Zebrafish Ptenb regulates protrusive activities of lateral mesendodermal cells but not prechordal plate cells during gastrulation. 29 Zebrafish Ptenb controls convergence and extension during gastrulation via controlling actin polymerization and downstream Akt1 and small GTPases. 31 ptenb-/- embryos shows convergence and extension defects by ptenb tMO1 32 References 34 Figures 42 Figure 1. Sequence analysis of the zebrafish ptenb gene. 43 Figure 2. Ptenb functions non cell-autonomously to regulate cell protrusions and cell migration. 45 Figure 3. Partial rescue of ptenb MO-induced defects by dominant-negative Cdc42. 46 Figure 4. Partial rescue of ptenb MO-induced defects by dominant-negative Rac1. 47 Figure 5. Over-expressing human constitutively active AKT1 (caAKT1) caused convergence and extension defects. 48 Figure 6. PIP3 detection by PH(Akt)-GFP mRNA 200 pg co-injection with StdMO 10 ng or ptenb tMO1 10 ng. 50 Figure 7. The ptenb tMO1 also induces convergence and extension defects in ptenb-/- embryos. 51 Figure 8. Signaling pathway of PI3 kinase coordinates with Ptenb. 52 Appendix 53 Materials and Methods 53 RNA isolation and RT-PCR analysis 53 DIC time-lapse cell migration recording 53 PI3-kinase inhibitor (LY294002) treatment 54 Actin polymerization assay 54 Figures 56 Figure S1. The ptenb translational-blocking morpholino oligonucleotide (tMO) caused the aberrant of Ptenb protein translation and further affected the zebrafish convergence and extension during gastrulation. 56 Figure S2. Expression patterns of zebrafish ptenb. 58 Figure S3. Rescue the ptenb morphant by PI3 kinase inhibitor LY294002. 59 Figure S4. Knockdown of ptenb inhibits cell protrusion formation of lateral hypoblast cells but not prechordal cells. 61 Figure S5. Knockdown of ptenb enhanced actin polymerization. 62 | |
| dc.language.iso | en | |
| dc.subject | PTEN | zh_TW |
| dc.subject | 原腸腔 | zh_TW |
| dc.subject | 斑馬魚 | zh_TW |
| dc.subject | PI3 kinase | zh_TW |
| dc.subject | 細胞遷移 | zh_TW |
| dc.subject | Pten | en |
| dc.subject | convergence and extension | en |
| dc.subject | gastrulation | en |
| dc.subject | PI3 kinase | en |
| dc.subject | zebrafish | en |
| dc.title | PTENB 調控斑馬魚原腸期胚細胞方向性遷移 | zh_TW |
| dc.title | PTENB Mediates Cell Migration during Gastrulation in
Zebrafish | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許文明,顏裕庭,蕭崇德 | |
| dc.subject.keyword | 原腸腔,斑馬魚,PI3 kinase,細胞遷移,PTEN, | zh_TW |
| dc.subject.keyword | gastrulation,PI3 kinase,zebrafish,Pten,convergence and extension, | en |
| dc.relation.page | 62 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-08-18 | |
| dc.contributor.author-college | 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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