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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22190完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張百恩 | |
| dc.contributor.author | Peng-Jen Kao | en |
| dc.contributor.author | 高鵬荏 | zh_TW |
| dc.date.accessioned | 2021-06-08T04:13:36Z | - |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-16 | |
| dc.identifier.citation | Amato, M.A., Boy, S., and Perron, M. (2004). Hedgehog signaling in vertebrate eye
development: a growing puzzle. Cell Mol Life Sci 61, 899-910. Ball, E.M., and Risbridger, G.P. (2001). Activins as regulators of branching morphogenesis. Dev Biol 238, 1-12. Barnes, E.A., Kong, M., Ollendorff, V., and Donoghue, D.J. (2001). Patched1 interacts with cyclin B1 to regulate cell cycle progression. EMBO J 20, 2214-2223. Bibliowicz, J., and Gross, J.M. (2009). Expanded progenitor populations,vitreo-retinal abnormalities, and Muller glial reactivity in the zebrafish leprechaun/patched2 retina. BMC Dev Biol 9, 52. Bilotta, J., and Saszik, S. (2001). The zebrafish as a model visual system. Int J Dev Neurosci 19, 621-629. Bitgood, M.J., Shen, L., and McMahon, A.P. (1996). Sertoli cell signaling by Desert hedgehog regulates the male germline. Curr Biol 6, 298-304. Bottner, M., Krieglstein, K., and Unsicker, K. (2000). The transforming growth factor- betas: structure, signaling, and roles in nervous system development and functions. J Neurochem 75, 2227-2240. Cayuso, J., and Marti, E. (2005). Morphogens in motion: growth control of the neural tube. J Neurobiol 64, 376-387. Chamoun, Z., Mann, R.K., Nellen, D., von Kessler, D.P., Bellotto, M., Beachy, P.A., and Basler, K. (2001). Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal. Science 293, 2080-2084. Chang, H., Brown, C.W., and Matzuk, M.M. (2002). Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23, 787-823. Chow, R.L., and Lang, R.A. (2001). Early eye development in vertebrates. Annu Rev Cell Dev Biol 17, 255-296. de Crombrugghe, B., Lefebvre, V., and Nakashima, K. (2001). Regulatory mechanisms in the pathways of cartilage and bone formation. Curr Opin Cell Biol 13, 721-727. Derynck, R., and Zhang, Y.E. (2003). Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425, 577-584. Donovan, S.L., and Dyer, M.A. (2005). Regulation of proliferation during central nervous system development. Semin Cell Dev Biol 16, 407-421. Duenker, N. (2005). Transforming growth factor-beta (TGF-beta) and programmed cell death in the vertebrate retina. Int Rev Cytol 245, 17-43. Dyer, M.A., and Cepko, C.L. (2001). Regulating proliferation during retinal development. Nat Rev Neurosci 2, 333-342. Esteve, P., and Bovolenta, P. (2006). Secreted inducers in vertebrate eye development: more functions for old morphogens. Curr Opin Neurobiol 16, 13-19. Fan, H., and Khavari, P.A. (1999). Sonic hedgehog opposes epithelial cell cycle arrest. J Cell Biol 147, 71-76. Flugel-Koch, C., Ohlmann, A., Piatigorsky, J., and Tamm, E.R. (2002). Disruption of anterior segment development by TGF-beta1 overexpression in the eyes of transgenic mice. Dev Dyn 225, 111-125. Francis, P.J., and Moore, A.T. (1999). The lens. Eye (Lond) 13 ( Pt 3b), 393-394. Furuta, Y., and Hogan, B.L. (1998). BMP4 is essential for lens induction in the mouse embryo. Genes Dev 12, 3764-3775. Gordon-Thomson, C., de Iongh, R.U., Hales, A.M., Chamberlain, C.G., and McAvoy, J.W. (1998). Differential cataractogenic potency of TGF-beta1, -beta2, and -beta3 and their expression in the postnatal rat eye. Invest Ophthalmol Vis Sci 39, 1399-1409. Graw, J. (2003). The genetic and molecular basis of congenital eye defects. Nat Rev Genet 4, 876-888. Harrison, C.A., Wiater, E., Gray, P.C., Greenwald, J., Choe, S., and Vale, W. (2004). Modulation of activin and BMP signaling. Mol Cell Endocrinol 225, 19-24. Hellemans, J., Coucke, P.J., Giedion, A., De Paepe, A., Kramer, P., Beemer, F., and Mortier, G.R. (2003). Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips. Am J Hum Genet 72, 1040-1046. Hooper, J.E., and Scott, M.P. (2005). Communicating with Hedgehogs. Nat Rev Mol Cell Biol 6, 306-317. Huangfu, D., and Anderson, K.V. (2006). Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development 133, 3-14. Ingham, P.W., and McMahon, A.P. (2001). Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15, 3059-3087. Ittner, L.M., Wurdak, H., Schwerdtfeger, K., Kunz, T., Ille, F., Leveen, P., Hjalt, T.A., Suter, U., Karlsson, S., Hafezi, F., et al. (2005). Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells. J Biol 4, 11. Jessell, T.M. (2000). Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1, 20-29. Kalderon, D. (2004). Hedgehog signaling: Costal-2 bridges the transduction gap. Curr Biol 14, R67-69. Kimelman, D., and Griffin, K.J. (2000). Vertebrate mesendoderm induction and patterning. Curr Opin Genet Dev 10, 350-356. Knight, P.G. (1996). Roles of inhibins, activins, and follistatin in the female reproductive system. Front Neuroendocrinol 17, 476-509. Krieglstein, K., Strelau, J., Schober, A., Sullivan, A., and Unsicker, K. (2002). TGF-beta and the regulation of neuron survival and death. J Physiol Paris 96, 25-30. Livesey, F.J., and Cepko, C.L. (2001). Vertebrate neural cell-fate determination: lessons from the retina. Nat Rev Neurosci 2, 109-118. Lum, L., and Beachy, P.A. (2004). The Hedgehog response network: sensors, switches, and routers. Science 304, 1755-1759. Marti, E., and Bovolenta, P. (2002). Sonic hedgehog in CNS development: one signal, multiple outputs. Trends Neurosci 25, 89-96. Martinez-Morales, J.R., Rodrigo, I., and Bovolenta, P. (2004). Eye development: a view from the retina pigmented epithelium. Bioessays 26, 766-777. Masland, R.H. (2001). The fundamental plan of the retina. Nat Neurosci 4, 877-886. Massague, J. (2000). How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1, 169-178. Massague, J. (2003). Integration of Smad and MAPK pathways: a link and a linker revisited. Genes Dev 17, 2993-2997. Massague, J., Seoane, J., and Wotton, D. (2005). Smad transcription factors. Genes Dev 19, 2783-2810. Mill, P., Mo, R., Fu, H., Grachtchouk, M., Kim, P.C., Dlugosz, A.A., and Hui, C.C. (2003). Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development. Genes Dev 17, 282-294. Moshiri, A., Close, J., and Reh, T.A. (2004). Retinal stem cells and regeneration. Int J Dev Biol 48, 1003-1014. Moshiri, A., McGuire, C.R., and Reh, T.A. (2005). Sonic hedgehog regulates proliferation of the retinal ciliary marginal zone in posthatch chicks. Dev Dyn 233, 66-75. Neuhauss, S.C. (2003). Behavioral genetic approaches to visual system development and function in zebrafish. J Neurobiol 54, 148-160. Nusslein-Volhard, C., and Wieschaus, E. (1980). Mutations affecting segment number and polarity in Drosophila. Nature 287, 795-801. Nybakken, K., and Perrimon, N. (2002). Hedgehog signal transduction: recent findings. Curr Opin Genet Dev 12, 503-511. O'Connor, M.B., Umulis, D., Othmer, H.G., and Blair, S.S. (2006). Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing. Development 133, 183-193. Oliver, G., and Gruss, P. (1997). Current views on eye development. Trends Neurosci 20, 415-421. Padgett, R.W., and Patterson, G.I. (2001). New developments for TGFbeta. Dev Cell 1, 343-349. Pagan-Westphal, S.M., and Tabin, C.J. (1998). The transfer of left-right positional information during chick embryogenesis. Cell 93, 25-35. Panman, L., and Zeller, R. (2003). Patterning the limb before and after SHH signalling. J Anat 202, 3-12. Sampath, K., Cheng, A.M., Frisch, A., and Wright, C.V. (1997). Functional differences among Xenopus nodal-related genes in left-right axis determination. Development 124, 3293-3302. Sariola, H., and Saarma, M. (2003). Novel functions and signalling pathways for GDNF. J Cell Sci 116, 3855-3862. Schier, A.F., and Shen, M.M. (2000). Nodal signalling in vertebrate development. Nature 403, 385-389. Siegel, P.M., and Massague, J. (2003). Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer 3, 807-821. Srinivasan, Y., Lovicu, F.J., and Overbeek, P.A. (1998). Lens-specific expression of transforming growth factor beta1 in transgenic mice causes anterior subcapsular cataracts. J Clin Invest 101, 625-634. Torroja, C., Gorfinkiel, N., and Guerrero, I. (2005). Mechanisms of Hedgehog gradient formation and interpretation. J Neurobiol 64, 334-356. Unsicker, K., Meier, C., Krieglstein, K., Sartor, B.M., and Flanders, K.C. (1996). Expression, localization, and function of transforming growth factor-beta s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia. J Neurobiol 29, 262-276. Varjosalo, M., and Taipale, J. (2007). Hedgehog signaling. J Cell Sci 120, 3-6. Varjosalo, M., and Taipale, J. (2008). Hedgehog: functions and mechanisms. Genes Dev 22, 2454-2472. Wakefield, L.M., and Roberts, A.B. (2002). TGF-beta signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev 12, 22-29. Wawersik, S., Purcell, P., Rauchman, M., Dudley, A.T., Robertson, E.J., and Maas, R. (1999). BMP7 acts in murine lens placode development. Dev Biol 207, 176-188. Whitman, M. (1998). Smads and early developmental signaling by the TGFbeta superfamily. Genes Dev 12, 2445-2462. Wijgerde, M., Ooms, M., Hoogerbrugge, J.W., and Grootegoed, J.A. (2005). Hedgehog signaling in mouse ovary: Indian hedgehog and desert hedgehog from granulosa cells induce target gene expression in developing theca cells. Endocrinology 146, 3558-3566. Yang, X.J. (2004). Roles of cell-extrinsic growth factors in vertebrate eye pattern formation and retinogenesis. Semin Cell Dev Biol 15, 91-103. Yingling, J.M., Blanchard, K.L., and Sawyer, J.S. (2004). Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3, 1011-1022. 王偉庭 (2005) 利用基因轉殖異位超量表現方法分析Sonic Hedgehog在斑馬魚 眼睛視網膜發育過程中所扮演之功能。國立台灣大學口腔生物科學研究所碩士論文。 黃崧威 (2006) 利用基因轉殖過量表現或抑制方法探討Transforming Growth Factor‐β3和Sonic Hedgehog在斑馬魚顱顏組織眼睛發育之功能。國立台灣大學口腔生物科學研究所碩士論文。 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22190 | - |
| dc.description.abstract | Transforming growth factor-β family (TGF-β family)和Sonic Hedgehog在胚胎的早期發育都扮演很重要的角色。以神經管發育為例，TGF-β family在神經管的背部大量表現，Sonic Hedgehog則在神經管的腹面大量表現，這兩種基因產物同時以濃度梯度的方式，向神經管方向擴散並且影響神經管的發育。
在本研究中，我想要探討TGF-β family和Sonic Hedgehog在眼睛的發育中扮演什麼樣的角色。在Shh方面，先前的研究結果(王偉庭, 2005)－βB1晶體蛋白(βB1-crystallin)啟動子在斑馬魚水晶體異位過量表現Shh。觀察所篩選到的轉殖恆定品系19號，發現眼睛視網膜外形呈球狀，不同於野生型的杯狀。而組織切片分析，發現視網膜細胞在CMZ (ciliary marginal zone)區域似乎有增生的現象，然而神經視網膜的分層是否有顯著的影響，則需進行Immunohistochemistry來證明。而TGF-β部分，之前的實驗結果（黃嵩崴,2006）－βB1晶體蛋白(βB1-crystallin)啟動子在斑馬魚水晶體異位過量表現TGF-β，發現在轉殖恆定品系4號的眼睛外觀上，瞳孔有變小的現象，而且將受精後7天的水晶體取下，發現水晶體也比野生型小。此外，除了水晶體大小發生異常之外，也發現在透明的水晶體中央出現混濁且不透明的區域，此為白內障形成的現象。 因此，從先前實驗結果推測Shh可能會對視網膜細胞的增生有所影響，而TGF-β3則影響水晶體的發育，甚至與白內障的形成有關。我在本實驗中便是運用immunohistochemistry、in situ hybridization等方法來了解TGF-β3或Shh在眼睛發育中所扮演的角色。綜合了以上實驗的結果，我發現在Shh異位過量表現的斑馬魚中，其眼睛視網膜的細胞分層並沒有明顯的改變；而在TGF-β3異位過量表現的斑馬魚中，的確有偵測到TGF-β3下游分子的表現。 從目前的實驗結果推論，推測TGF-β3和Shh對於斑馬魚眼睛組織扮演不同的調控角色。TGF-β3的過量表現會影響水晶體的發育，造成白內障的形成。而Shh則是對視網膜細胞的分層並沒有影響，但似乎會造成CMZ區域的增生。而在我所進行的實驗中，對於CMZ是否增生並沒有具體化的結論，但這一部分還必須重複上述實驗才能證明。 | zh_TW |
| dc.description.abstract | Transforming growth factor-β family (TGF-β family) and Sonic Hedgehog play critical roles in early developmental processes of embryo. For example, TGF-β family is expressed in the dorsal neural tube, whereas Sonic Hedgehog is expressed in the ventral neural tube. Both proteins diffuse and pattern the neural tube depending on the function of the concentration gradient.
In this study, I want to elucidate the function of TGF-β family and Sonic Hedgehog in the eye development of zebrafish. According to the previous result (Wang, 2005)-using zebrafish lens-specific βB1-Crystallin 1.3 kb promoter fragment (Cr1.3) to drive ectopic overexpression of Shh in the lens, I observed the stable transgenic zebrafish line No.19 for study. I found that the silhouette of retina has changed. Through sectioning, it seems that the CMZ (ciliary marginal zone) has proliferated. And Shh may affect the stratification of neural retina in the line No.19, which depends on the result of Immunohistochemistry to prove it. In TGF-β, according to the previous result (Huang, 2006)-using zebrafish lens- specific βB1-Crystallin 1.3 kb promoter fragment (Cr1.3) to drive ectopic overexpression of TGF-β in the lens, I observed the stable transgenic zebrafish line No.30 for study. I found the pupil of the No.30 stable line seemed to be smaller than wild type fish. Then I excised the lens out of 7 days-post- fertilization (7 dpf) embryo and found the lens was indeed smaller than those of wild type fish. In addition to the abnormal lens size, I also observed that there was a cloudy and opaque region in the eye lens. In the previous results, Shh may affect the proliferation of neural retina cells. And TGF-β3 could influence the lens development, even implicated in the occurrence of cataract. In this study, I use in situ hybridization and immunohistochemistry methods to elucidate the function of TGF-β3 and Shh during the eye development of zebrafish. Conclusively, I found the stratification of neural retina in Shh overexpression zebrafish does not change. And the downstream molecules of TGF-β3 are detected in TGF-β3 overexpression zebrafish. In the preliminary results, TGF-β family and Shh may play different roles in regulating the eye development of zebrafish. TGF-β3 influence the lens development, and implicated in the occurrence of cataract. And Shh do not affect the stratification of neural retina, but result in the expanded CMZ. In my study, we do not have conclusive result. In the future, I have to repeat this method to prove it. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T04:13:36Z (GMT). No. of bitstreams: 1 ntu-99-R97450007-1.pdf: 6613707 bytes, checksum: 547079d68f4461783e6ed78a09bdbe6d (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 口試委員審定書…………………………………….……………......i
中文摘要…………………………………………………………………ii 英文摘要……………....………………………………………………iv 壹、前言…………………………………………………………………1 貳、實驗材料……………………………………………………………24 參、實驗方法……………………………………………………………31 肆、結果…………………………………………………………………39 伍、討論…………………………………………………………………43 陸、圖表…………………………………………………………………47 參考文獻..………………………………………………………………65 | |
| dc.language.iso | zh-TW | |
| dc.subject | 白內障 | zh_TW |
| dc.subject | Sonic hedgehog | zh_TW |
| dc.subject | 轉化生長因子β | zh_TW |
| dc.subject | 視網膜發育 | zh_TW |
| dc.subject | 水晶體發育 | zh_TW |
| dc.subject | cataract | en |
| dc.subject | Sonic hedgehog | en |
| dc.subject | Transforming growth factor-β | en |
| dc.subject | retina development | en |
| dc.subject | lens development | en |
| dc.title | 利用免疫組織染色和原位雜交反應探討TGFβ3和Shh在轉殖斑馬魚眼睛發育過程所扮演的角色 | zh_TW |
| dc.title | Functional Analyses of TGFβ3 and Shh during Eye Development of Transgenic Zebrafish by Immunohistochemistry and in situ Hybridization | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳志成,姚宗珍 | |
| dc.subject.keyword | Sonic hedgehog,轉化生長因子β,視網膜發育,水晶體發育,白內障, | zh_TW |
| dc.subject.keyword | Sonic hedgehog,Transforming growth factor-β,retina development,lens development,cataract, | en |
| dc.relation.page | 71 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2010-08-16 | |
| dc.contributor.author-college | 牙醫專業學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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