請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25197完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡懷楨 | |
| dc.contributor.author | Ying-Fang Su | en |
| dc.contributor.author | 蘇盈方 | zh_TW |
| dc.date.accessioned | 2021-06-08T06:04:57Z | - |
| dc.date.copyright | 2011-08-12 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-05 | |
| dc.identifier.citation | Annes, J. P., Munger, J. S. and Rifkin, D. B. (2003). Making sense of latent TGFb activation. J Cell Sci 116, 217-24.
Aravind, L. and Koonin, E. V. (1998). A colipase fold in the carboxy-terminal domain of the Wnt antagonists--the Dickkopfs. Curr Biol 8, R477-8. Bajanca, F., Luz, M., Duxson, M. J. and Thorsteinsdottir, S. (2004). Integrins in the mouse myotome: developmental changes and differences between the epaxial and hypaxial lineage. Dev Dyn 231, 402-15. Bajanca, F., Luz, M., Raymond, K., Martins, G. G., Sonnenberg, A., Tajbakhsh, S., Buckingham, M. and Thorsteinsdottir, S. (2006). Integrin a6b1-laminin interactions regulate early myotome formation in the mouse embryo. Development 133, 1635-44. Barrantes Idel, B., Montero-Pedrazuela, A., Guadano-Ferraz, A., Obregon, M. J., Martinez de Mena, R., Gailus-Durner, V., Fuchs, H., Franz, T. J., Kalaydjiev, S., Klempt, M. et al. (2006). Generation and characterization of dickkopf3 mutant mice. Mol Cell Biol 26, 2317-26. Blaschuk, K. L. and Holland, P. C. (1994). The regulation of a5b1 integrin expression in human muscle cells. Dev Biol 164, 475-83. Boettiger, D., Enomoto-Iwamoto, M., Yoon, H. Y., Hofer, U., Menko, A. S. and Chiquet-Ehrismann, R. (1995). Regulation of integrin a5b1 affinity during myogenic differentiation. Dev Biol 169, 261-72. Bronner-Fraser, M., Artinger, M., Muschler, J. and Horwitz, A. F. (1992). Developmentally regulated expression of a6 integrin in avian embryos. Development 115, 197-211. Brott, B. K. and Sokol, S. Y. (2002). Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins. Mol Cell Biol 22, 6100-10. Buckingham, M. and Relaix, F. (2007). The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions. Annu Rev Cell Dev Biol 23, 645-73. Burkhalter, R. J., Symowicz, J., Hudson, L. G., Gottardi, C. J. and Stack, M. S. (2011). Integrin Regulation of b-Catenin Signaling in Ovarian Carcinoma. J Biol Chem 286, 23467-75. Cadigan, K. M. and Nusse, R. (1997). Wnt signaling: a common theme in animal development. Genes Dev 11, 3286-305. Chen, Y. H., Lee, W. C., Liu, C. F. and Tsai, H. J. (2001). Molecular structure, dynamic expression, and promoter analysis of zebrafish (Danio rerio) myf-5 gene. Genesis 29, 22-35. Choi, J., Costa, M. L., Mermelstein, C. S., Chagas, C., Holtzer, S. and Holtzer, H. (1990). MyoD converts primary dermal fibroblasts, chondroblasts, smooth muscle, and retinal pigmented epithelial cells into striated mononucleated myoblasts and multinucleated myotubes. Proc Natl Acad Sci U S A 87, 7988-92. Chong, S. W., Korzh, V. and Jiang, Y. J. (2009). Myogenesis and molecules - insights from zebrafish Danio rerio. J Fish Biol 74, 1693-755. Coutelle, O., Blagden, C. S., Hampson, R., Halai, C., Rigby, P. W. and Hughes, S. M. (2001). Hedgehog signalling is required for maintenance of myf5 and myoD expression and timely terminal differentiation in zebrafish adaxial myogenesis. Dev Biol 236, 136-50. Cui, C. Y., Kunisada, M., Piao, Y., Childress, V., Ko, M. S. and Schlessinger, D. (2010). Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair. PLoS One 5, e10009. Davidson, G., Mao, B., del Barco Barrantes, I. and Niehrs, C. (2002). Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning. Development 129, 5587-96. Davis, R. L., Weintraub, H. and Lassar, A. B. (1987). Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987-1000. Hashimoto, H., Itoh, M., Yamanaka, Y., Yamashita, S., Shimizu, T., Solnica-Krezel, L., Hibi, M. and Hirano, T. (2000). Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation. Dev Biol 217, 138-52. He, X., Semenov, M., Tamai, K. and Zeng, X. (2004). LDL receptor-related proteins 5 and 6 in Wnt/b-catenin signaling: arrows point the way. Development 131, 1663-77. Hinits, Y., Osborn, D. P., Carvajal, J. J., Rigby, P. W. and Hughes, S. M. (2007). Mrf4 (myf6) is dynamically expressed in differentiated zebrafish skeletal muscle. Gene Expr Patterns 7, 738-45. Hirsch, E., Gullberg, D., Balzac, F., Altruda, F., Silengo, L. and Tarone, G. (1994). av integrin subunit is predominantly located in nervous tissue and skeletal muscle during mouse development. Dev Dyn 201, 108-20. Hsu, R. J., Lin, C. C., Su, Y. F. and Tsai, H. J. (2011). dickkopf-3-related gene regulates the expression of zebrafish myf5 gene through phosphorylated p38a-dependent Smad4 activity. J Biol Chem 286, 6855-64. Hsu, R. J., Lin, C. Y., Hoi, H. S., Zheng, S. K., Lin, C. C. and Tsai, H. J. (2010). Novel intronic microRNA represses zebrafish myf5 promoter activity through silencing dickkopf-3 gene. Nucleic Acids Res 38, 4384-93. Hynes, R. O. (1987). Integrins: a family of cell surface receptors. Cell 48, 549-54. Hynes, R. O. (1992). Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69, 11-25. Hynes, R. O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-87. Ivaska, J., Reunanen, H., Westermarck, J., Koivisto, L., Kahari, V. M. and Heino, J. (1999). Integrin a2b1 mediates isoform-specific activation of p38 and upregulation of collagen gene transcription by a mechanism involving the a2 cytoplasmic tail. J Cell Biol 147, 401-16. Johnson, M. S., Lu, N., Denessiouk, K., Heino, J. and Gullberg, D. (2009). Integrins during evolution: evolutionary trees and model organisms. Biochim Biophys Acta 1788, 779-89. Kablar, B., Krastel, K., Ying, C., Asakura, A., Tapscott, S. J. and Rudnicki, M. A. (1997). MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle. Development 124, 4729-38. Kataoka, K., Sakaguchi, M., Li, K. P., Taketa, C., Yamamoto, K., Du, G., Funahashi, H., Murata, H. and Huh, N. H. (2010). Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues. Int J Mol Med 26, 853-9. Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B. and Schilling, T. F. (1995). Stages of embryonic development of the zebrafish. Dev Dyn 203, 253-310. Kohn, M. J., Kaneko, K. J. and DePamphilis, M. L. (2005). DkkL1 (Soggy), a Dickkopf family member, localizes to the acrosome during mammalian spermatogenesis. Mol Reprod Dev 71, 516-22. Krupnik, V. E., Sharp, J. D., Jiang, C., Robison, K., Chickering, T. W., Amaravadi, L., Brown, D. E., Guyot, D., Mays, G., Leiby, K. et al. (1999). Functional and structural diversity of the human Dickkopf gene family. Gene 238, 301-13. Li, L., Mao, J., Sun, L., Liu, W. and Wu, D. (2002). Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled. J Biol Chem 277, 5977-81. Li, X., Liu, P., Liu, W., Maye, P., Zhang, J., Zhang, Y., Hurley, M., Guo, C., Boskey, A., Sun, L. et al. (2005). Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet 37, 945-52. Lin, C. Y., Chen, Y. H., Lee, H. C. and Tsai, H. J. (2004). Novel cis-element in intron 1 represses somite expression of zebrafish myf-5. Gene 334, 63-72. MacDonald, B. T., Adamska, M. and Meisler, M. H. (2004). Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6. Development 131, 2543-52. Mao, B. and Niehrs, C. (2003). Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling. Gene 302, 179-83. Mao, B., Wu, W., Davidson, G., Marhold, J., Li, M., Mechler, B. M., Delius, H., Hoppe, D., Stannek, P., Walter, C. et al. (2002). Kremen proteins are Dickkopf receptors that regulate Wnt/b-catenin signalling. Nature 417, 664-7. Mao, B., Wu, W., Li, Y., Hoppe, D., Stannek, P., Glinka, A. and Niehrs, C. (2001). LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature 411, 321-5. Margadant, C. and Sonnenberg, A. (2010). Integrin-TGF-b crosstalk in fibrosis, cancer and wound healing. EMBO Rep 11, 97-105. Massague, J. and Chen, Y. G. (2000). Controlling TGF-b signaling. Genes Dev 14, 627-44. Mu, D., Cambier, S., Fjellbirkeland, L., Baron, J. L., Munger, J. S., Kawakatsu, H., Sheppard, D., Broaddus, V. C. and Nishimura, S. L. (2002). The integrin avb8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-b1. J Cell Biol 157, 493-507. Mukhopadhyay, M., Gorivodsky, M., Shtrom, S., Grinberg, A., Niehrs, C., Morasso, M. I. and Westphal, H. (2006). Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium. Development 133, 2149-54. Mukhopadhyay, M., Shtrom, S., Rodriguez-Esteban, C., Chen, L., Tsukui, T., Gomer, L., Dorward, D. W., Glinka, A., Grinberg, A., Huang, S. P. et al. (2001). Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev Cell 1, 423-34. Parr, B. A. and McMahon, A. P. (1994). Wnt genes and vertebrate development. Curr Opin Genet Dev 4, 523-8. Pechkovsky, D. V., Scaffidi, A. K., Hackett, T. L., Ballard, J., Shaheen, F., Thompson, P. J., Thannickal, V. J. and Knight, D. A. (2008). Transforming growth factor b1 induces avb3 integrin expression in human lung fibroblasts via a b3 integrin-, c-Src-, and p38 MAPK-dependent pathway. J Biol Chem 283, 12898-908. Pinho, S. and Niehrs, C. (2007). Dkk3 is required for TGF-b signaling during Xenopus mesoderm induction. Differentiation 75, 957-67. Pownall, M. E., Gustafsson, M. K. and Emerson, C. P., Jr. (2002). Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annu Rev Cell Dev Biol 18, 747-83. Puri, P. L. and Sartorelli, V. (2000). Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and post-transcriptional modifications. J Cell Physiol 185, 155-73. Sastry, S. K., Lakonishok, M., Wu, S., Truong, T. Q., Huttenlocher, A., Turner, C. E. and Horwitz, A. F. (1999). Quantitative changes in integrin and focal adhesion signaling regulate myoblast cell cycle withdrawal. J Cell Biol 144, 1295-309. Schwander, M., Leu, M., Stumm, M., Dorchies, O. M., Ruegg, U. T., Schittny, J. and Muller, U. (2003). b1 integrins regulate myoblast fusion and sarcomere assembly. Dev Cell 4, 673-85. Segat, D., Comai, R., Di Marco, E., Strangio, A., Cancedda, R., Franzi, A. T. and Tacchetti, C. (2002). Integrins a6Ab1 and a6Bb1 promote different stages of chondrogenic cell differentiation. J Biol Chem 277, 31612-22. Semenov, M. V., Tamai, K., Brott, B. K., Kuhl, M., Sokol, S. and He, X. (2001). Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol 11, 951-61. Shattil, S. J., Kim, C. and Ginsberg, M. H. (2010). The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol 11, 288-300. Song, W. K., Wang, W., Foster, R. F., Bielser, D. A. and Kaufman, S. J. (1992). H36-a7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis. J Cell Biol 117, 643-57. Song, W. K., Wang, W., Sato, H., Bielser, D. A. and Kaufman, S. J. (1993). Expression of a7 integrin cytoplasmic domains during skeletal muscle development: alternate forms, conformational change, and homologies with serine/threonine kinases and tyrosine phosphatases. J Cell Sci 106 ( Pt 4), 1139-52. Takada, Y., Ye, X. and Simon, S. (2007). The integrins. Genome Biol 8, 215. Thisse, C. and Thisse, B. (2008). High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc 3, 59-69. Tidball, J. G. (1992). Desmin at myotendinous junctions. Exp Cell Res 199, 206-12. Vachon, P. H., Xu, H., Liu, L., Loechel, F., Hayashi, Y., Arahata, K., Reed, J. C., Wewer, U. M. and Engvall, E. (1997). Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy. J Clin Invest 100, 1870-81. Weinberg, E. S., Allende, M. L., Kelly, C. S., Abdelhamid, A., Murakami, T., Andermann, P., Doerre, O. G., Grunwald, D. J. and Riggleman, B. (1996). Developmental regulation of zebrafish MyoD in wild-type, no tail and spadetail embryos. Development 122, 271-80. White, D. E., Cardiff, R. D., Dedhar, S. and Muller, W. J. (2001). Mammary epithelial-specific expression of the integrin-linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice. Oncogene 20, 7064-72. Wodarz, A. and Nusse, R. (1998). Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol 14, 59-88. Yao, C. C., Ziober, B. L., Sutherland, A. E., Mendrick, D. L. and Kramer, R. H. (1996). Laminins promote the locomotion of skeletal myoblasts via the alpha 7 integrin receptor. J Cell Sci 109 ( Pt 13), 3139-50. Yusuf, F. and Brand-Saberi, B. (2006). The eventful somite: patterning, fate determination and cell division in the somite. Anat Embryol (Berl) 211 Suppl 1, 21-30. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25197 | - |
| dc.description.abstract | Myf5是肌肉發育調控因子MRFs (myogenic regulatory factors) 的成員，對於肌肉發育的特化和分化上具有重要功能。斑馬魚myf5 intron I中含有miR-3906，會抑制其目標基因dickkopf-3-related gene (dkk3r) 的mRNA轉譯。Dkk3r為外泌型蛋白質，會調控細胞質訊息傳遞路徑，使得下游p38a磷酸化比例增加，進而增加Smad4蛋白質穩定性，進一步促使Smad2/Smad3a/Smad4複合體形成，進入細胞核以活化myf5啟動子，影響體節肌肉的生成發育。然而外泌型的Dkk3r是藉由與何種膜蛋白受器結合來調控胚胎發育仍然為未知。Fu (unpublished data) 以昆蟲細胞大量表現斑馬魚Dkk3r-Flag蛋白質，於斑馬魚總蛋白質中藉由蛋白質免疫沉澱實驗和蛋白質質譜分析篩選出Integrin alpha6b (Itga6b) 為可能結合的膜蛋白受器基因之一。為了進一步確認這個假設，本實驗中首先以whole-mount in situ hybridization (WISH) 觀察dkk3r mRNA與itga6b mRNA表現位置，發現於肌肉發育時期 (16 hpf) 兩者mRNA在體節位置皆有表現。在HEK-293T細胞中進行in vitro cell surface binding assay則可以偵測到Dkk3r與Itga6b的表現訊號位置在細胞膜有co-localization的情形。顯示於時間及空間上Dkk3r與Itga6b都相重疊。接下來，利用in vivo luciferase assay可以發現，於斑馬魚胚胎中過量表現dkk3r mRNA可以使得myf5啟動子所驅動的luciferase活性上升為223％，而過量表現itga6b mRNA可使得其活性上升為217%。另外，若dkk3r mRNA以及itga6b mRNA共同過量表現時，會使myf5啟動子驅動luciferase的活性有加成上升為397%的效力。上述活性上升皆有dosage-dependent的現象。而當過量表現itga6b mRNA並同時共同注射dkk3r-MO 去抑制Dkk3r的表現時，會造成myf5啟動子驅動luciferase活性下降為69%。這些證據顯示斑馬魚胚胎中Itga6b開啟下游的活性需要Dkk3r來參與。另一方面，注射itga6b-MO以抑制Itga6b的表現，可觀察到斑馬魚胚胎體節形狀異常；進而利用WISH也可以觀察到抑制Itg alpha 6b的表現，會使得myf5 mRNA於16 hpf時在體節表現剩下三節 (-II、-I、0) 且表現量較少，甚至有不表現的缺失。更進一步的證實Itga6b的缺失會使得Dkk3r下游之磷酸化p38a蛋白質的表現量下降。綜合以上實驗結果，我們認為Itga6b極可能為Dkk3r的膜蛋白受器，而兩者間會互相結合開啟下游訊息傳遞路徑，進而調控斑馬魚胚胎發育時期在體節內myf5啟動子的活性。 | zh_TW |
| dc.description.abstract | Myf5, one of the myogenic regulatory factors, plays important roles in the specification and differentiation of muscular cells during myogenesis. In zebrafish, an intronic microRNA (miR), miR-3906, located within myf5 intron I, has been reported to silence the translation of its target gene, dickkopf-3-related (dkk3r) gene. Dkk3r, a secretory protein, regulates the phosporylation of p38a to maintain Smad4 stability, which, in turn, enabling the Smad2/Smad3a/Smad4 complex to form and to activate the myf5 promoter in nucleus. However, the membrane receptor(s) bound by Dkk3r to control signal transduction is still unknown. After recombinant zebrafish Dkk3r tagged with Flag was produced by insect cells, we applied protein immunoprecipitation and mass spectromotry to screen the putative receptors of Dkk3r. We found that Integrin alpha 6b (Itga6b) might be one of receptors to interact with Dkk3r. To further confirm this hypothesis, we used whole-mount in situ hybridization and found that the transcripts of both dkk3r and itga6b were presented in somites at 16 hpf during myogenesis. By in vitro cell surface binding assay, we also observed that Dkk3r and Itga6b were co-expressed at the cell membrane of HEK-293T, indicating that the temporal and spatial expressions of dkk3r and itga6b are co-localized. Furthermore, in vivo luciferase assay demonstrated that the luciferase activity driven by myf5 promoter was 223% and 217% greater than that of control when the excessive dkk3r and itga6b mRNAs were injected into embryos, respectively. Interestingly, when we co-injected dkk3r and itga6b mRNAs into embryos, the luciferase activity was up-regulated as high as 397% greater than that of control embryos. This up-regulation of myf5 promoter activity mediated by interaction between dkk3r and itga6b was dosage-dependent. In contrast, when dkk3r was knockdown and co-injected with itga6b mRNA, the luciferase activity was down-regulated to 69% of control embryos, suggesting that the regulatory effect of Itga6b on the downstream activity is dependent on Dkk3r signal pathway. In addition, knockdown of itga6b by injection of itga6b-morpholinos resulted in abnormal shape of somites and weak or even absent expression of myf5 in somites at 16 hpf. Furthermore, knockdown of itga6b reduced the protein level of the phosphorylated p38a. Taken together, we concluded that it is highly likely that Itga6b functions as a receptor of Dkk3r. Their interactions drive the downstream signal transduction to regulate myf5 promoter activity in somites during the development of zebrafish embryos. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T06:04:57Z (GMT). No. of bitstreams: 1 ntu-100-R98B43002-1.pdf: 5569797 bytes, checksum: cfa84133b06dba210c7fb5669595db3d (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 目錄
中文摘要 ------------------------------------------- 1 英文摘要 ------------------------------------------- 3 文獻回顧 ------------------------------------------- 5 前言 ----------------------------------------------- 13 實驗材料與方法 ------------------------------------- 15 結果 ----------------------------------------------- 26 討論 ----------------------------------------------- 31 總結 ----------------------------------------------- 36 參考文獻 ------------------------------------------- 37 圖表 ----------------------------------------------- 44 附錄 ----------------------------------------------- 52 | |
| dc.language.iso | zh-TW | |
| dc.title | 斑馬魚Dickkopf-3-related gene (Dkk3r) 藉由膜蛋白受器Integrin alpha 6b影響肌肉調控蛋白myf5基因啟動子的活性 | zh_TW |
| dc.title | Zebrafish Dickkopf-3-related gene (Dkk3r) regulates the promoter activity of myogenic regulatory factor myf5 gene through interaction with membrane receptor of Integrin alpha 6b | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張震東,王文柄,楊啟伸 | |
| dc.subject.keyword | Dkk3r,Integrin alpha 6b,myf5,肌肉發育,斑馬魚, | zh_TW |
| dc.subject.keyword | Dkk3r,Integrin alpha 6b,myf5,myogenesis,zebrafish, | en |
| dc.relation.page | 56 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2011-08-05 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-100-1.pdf 目前未授權公開取用 | 5.44 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。