請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22511
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡懷楨 | |
dc.contributor.author | Hsing-Yen Huang | en |
dc.contributor.author | 黃倖妍 | zh_TW |
dc.date.accessioned | 2021-06-08T04:19:33Z | - |
dc.date.copyright | 2010-07-28 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-07-21 | |
dc.identifier.citation | Akiduki, S. and Ikemoto, M. J. (2008). Modulation of the neural glutamate transporter EAAC1 by the addicsin-interacting protein ARL6IP1. J Biol Chem. 283, 31323-31332.
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. Bajoghli, B., Aghaallaei, N., Heimbucher, T. and Czerny, T. (2004). An artificial promoter construct for heat-inducible misexpression during fish embryogenesis. Dev Biol. 271, 416-430. Beales, P. L., Elcioglu, N., Woolf, A. S., Parker, D. and Flinter, F. A. (1999). New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet. 36, 437-446. Bilotta, J. and Saszik, S. (2001). The zebrafish as a model visual system. Int J Dev Neurosci. 19, 621-629. Bischoff, F. R. and Ponstingl, H. (1991). Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide. Proc Natl Acad Sci U S A. 88, 10830-10834. Brockerhoff, S. E., Hurley, J. B., Janssen-Bienhold, U., Neuhauss, S. C., Driever, W. and Dowling, J. E. (1995). A behavioral screen for isolating zebrafish mutants with visual system defects. Proc Natl Acad Sci USA. 92:10545-10549. 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. Chiang, A. P., Nishimura, D., Searby, C., Elbedour, K., Carmi, R., Ferguson, A. L., Secrist, J., Braun, T., Casavant, T., Stone, E. M. and Sheffield, V. C. (2004). Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3). Am J Hum Genet. 75, 475-84. Chow, R. L. and Lang, R. A. (2001). Early eye development in vertebrates. Annu Rev Cell Dev Biol. 17, 255-296. Clark, J., Moore, L., Krasinskas, A., Way, J., Battey, J., Tamkun, J. and Kahn, R. A. (1993). Selective amplification of additional members of the ADP-ribosylation factor (ARF) family: cloning of additional human and Drosophila ARF-like genes. Proc Natl Acad Sci USA. 90, 8952-8956. Durand, B. and Raff, M. (2000). A cell-intrinsic timer that operates during oligodendrocyte development. Bioessays. 22, 64-71. Dyer, M. A. and Cepko, C. L. (2000). p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina. Development. 127, 3593-3605. Dyer, M. A. and Cepko, C. L. (2001a). p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J Neurosci. 21, 4259-4271. D'Souza-Schorey, C. and Chavrier, P. (2006). ARF proteins: roles in membrane traffic and beyond. Nat. Rev. Mol. Cell Biol. 7, 347-358. Fan, Y., Esmail, M. A., Ansley, S. J., Blacque, O. E., Boroevich, K., Ross, A. J., Moore, S. J., Badano, J. L., May-Simera, H., Compton, D. S., Green, J. S., Lewis, R. A., van Haelst, M. M., Parfrey, P. S., Baillie, D. L., Beales, P. L., Katsanis, N., Davidson, W. S. and Leroux, M. R. (2004). Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet. 36, 989-993. Fashena, D. and Westerfield, M. (1999). Secondary motoneuron axons localize DM-GRASP on their fasciculated segments. J Comp Neurol. 406, 415-424. Fischer, S., Prykhozhij, S., Rau, M. J. and Neumann, C. J. (2007). Mutation of zebrafish caf-1b results in S phase arrest, defective differentiation, and p53-mediated apoptosis during organogenesis. Cell Cycle. 6, 2962-2969. Hisanaga, E., Park, K. Y., Yamada, S., Hashimoto, H., Takeuchi, T., Mori, M., Seno, M., Umezawa, K., Takei, I. and Kojima, I. (2008). A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4. Endocr J. 55, 535-543. Hu, M. and Easter, S. S. (1999). Retinal neurogenesis: the formation of the initial central patch of postmitotic cells. Dev Biol. 207, 309-321. Huang, H. Y., Dai, E. S., Liu, J. T., Tu, C. T., Yang, T. C. and Tsai, H. J. (2009). The embryonic expression patterns and the knockdown phenotypes of zebrafish ADP-ribosylation factor-like 6 interacting protein gene. Dev Dyn. 238, 232-240. Hutchins, J. R., Moore, W. J. and Clarke, P. R. (2009). Dynamic localisation of Ran GTPase during the cell cycle. BMC Cell Biol. 10, 66. Ingham, P. W. and McMahon, A. P. (2001). Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15, 3059-3087. Ingley, E., Williams, J. H., Walker, C. E., Tsai, S., Colley, S., Sayer, M. S., Tilbrook, P. A., Sarna, M., Beaumont, J. G. and Klinken, S. P. (1999). A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61beta subunit. FEBS Lett. 459, 69-74. Jensen, A. M. and Wallace, V. A. (1997). Expression of Sonic hedgehog and its putative role as a precursor cell mitogen in the developing mouse retina. Development. 124, 363-371. Kay, J. N., Link, B. A. and Baier, H. (2005). Staggered cell-intrinsic timing of ath5 expression underlies the wave of ganglion cell neurogenesis in the zebrafish retina. Development. 132, 2573-2585. Keryer, G., Di Fiore, B., Celati, C., Lechtreck, K. F. Mogensen, M., Delouvee, A., Lavia, P., Bornens, M. and Tassin, A. M. (2003). Part of Ran is associated with AKAP450 at the centrosome: involvement in microtubule-organizing activity. Mol Biol Cell. 14, 4260-4271. Kim, C. H., Ueshima, E., Muraoka, O., Tanaka, H., Yeo, S. Y., Huh, T. L. and Miki, N. (1996). Zebrafish elav/HuC homologue as a very early neuronal marker. Neurosci Lett. 216, 109-112. 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. Lee, H. C., Huang, H. Y., Lin, C. Y., Chen, Y. H. and Tsai, H. J. (2006). Foxd3 mediates zebrafish myf5 expression during early somitogenesis. Dev Biol. 290, 359-372. Lee, H. C., Tsai, J. N., Liao, P. Y., Tsai, W. Y., Lin, K. Y., Chuang, C. C., Sun, C. K., Chang, W. C. and Tsai, H. J. (2007). Glycogen synthase kinase 3α and 3β have distinct functions during cardiogenesis of zebrafish embryo. BMC Dev Biol. 7, 93-107. Levine, E. M., Roelink, H., Turner, J. and Reh, T. A. (1997). Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro. J Neurosci. 17, 6277-6288. Lui, H. M., Chen, J., Wang, L. and Naumovski, L. (2003). ARMER, apoptotic regulator in the membrane of the endoplasmic reticulum, a novel inhibitor of apoptosis. Mol Cancer Res. 1, 508-518. Maroon, H., Walshe, J., Mahmood, R., Kiefer, P., Dickson, C. and Mason, I. (2002). Fgf3 and Fgf8 are required together for formation of the otic placode and vesicle. Development. 129, 2099-2108. Masai, I., Stemple, D. L., Okamoto, H. and Wilson, S. W. (2000). Midline signals regulate retinal neurogenesis in zebrafish. Neuron. 27, 251-263. Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peränen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C. and Jackson, P. K.(2007). A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell. 129, 1201-1213. Neumann, C. J. and Nuesslein-Volhard. C. (2000). Patterning of the zebrafish retina by a wave of sonic hedgehog activity. Science. 289, 2137-2139. Nomura, N., Nagase, T., Miyajima, N., Sazuka, T., Tanaka, A., Sato, S., Seki, N., Kawarabayasi, Y., Ishikawa, K. and Tabata, S. (1994). Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1, 223-229. Pettersson, M., Bessonova, M., Gu, H. F., Groop, L. C. and Jonsson, J. I. (2000). Characterization, chromosomal localization, and expression during hematopoietic differentiation of the gene encoding Arl6ip, ADP-ribosylation-like factor-6 interacting protein (ARL6). Genomics. 68, 351-354. Raymond, P. A., Barthel, L. K. and Curran, G. A. (1995). Developmental patterning of rod and cone photoreceptors in embryonic zebrafish. J Comp Neurol. 359, 537-550. Roy, S. and Ingham, P. W. (2002). Hedgehogs tryst with the cell cycle. J Cell Sci. 115, 4393-4397. Ryu, S., Holzschuh, J., Erhardt, S., Ettl, A. K. and Driever, W. (2005). Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis. Proc Natl Acad Sci U S A. 102, 18467-18472. Schauerte, H. E., van Eeden, F. J., Fricke, C., Odenthal, J., Strahle, U. and Haffter P. (1998). Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish. Development. 125, 2983-2993. Schmitt, E. A. and Dowling, J. E. (1994). Early eye morphogenesis in the zebrafish, Brachydanio rerio. J Comp Neurol. 344, 532-542. Schmitt, E.A. and Dowling, J. E. (1999). Early retinal development in the zebrafish, Danio rerio: light and electron microscopic analyses. J Comp Neurol. 404, 515-536. Shkumatava, A., Fischer, S., Muller, F., Strahle, U. and Neumann, C. J. (2004). Sonic hedgehog, secreted by amacrine cells, acts as a short-range signal to direct differentiation and lamination in the zebrafish retina. Development. 131, 3849-3858. Shkumatava, A. and Neumann, C. J. (2005). Shh directs cell-cycle exit by activating p57Kip2 in the zebrafish retina. EMBO Rep. 6, 563-569. Sidman, R. L. and Rakic, P. (1982). Development of the human central nervous system. In: Haymaker W, Adams RD (eds) Histology and Histopathology of the Nervous System, Vol. 1. Springfield: Thomas 3-145. Stenkamp, D. L., Frey, R. A., Mallory, D. E. and Shupe, E. E. (2002). Embryonic retinal gene expression in sonic-you mutant zebrafish. Dev Dyn. 225, 344-350. Suzuki, E., Ogura, H., Kato, K., Takei, I., Kabe, Y., Handa, H. and Umezawa, K. (2009). Preparation of conophylline affinity nano-beads and identification of a target protein. Bioorg Med Chem. 17, 6188-6195. Takada, T., Iida, K., Sasaki, H., Taira, M. and Kimura, H. (2005). Expression of ADP-ribosylation factor (ARF)-like protein 6 during mouse embryonic development. Int J Dev Biol. 49, 891-894. Tian, N. M. and Price, D. J. (2005). Why cavefish are blind. Bioessays. 27, 235-238. Tobin, J.L. and Beales, P.L. (2007). Bardet-Biedl syndrome: beyond the cilium. Pediatr. Nephrol. 22, 926-936. Westerfield, M. 1993. The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio rerio). Institute of Neuroscience, University of Oregon, Eugene, OR. 9.1-9.3pp. Westerfield, M. 1995. The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio rerio). Institute of Neuroscience, University of Oregon, Eugene, OR. 9.1-9.3pp. Wiens, C. J., Tong, Y., Esmail, M. A., Oh, E., Gerdes, J. M., Wang, J., Tempel, W., Rattner, J. B., Katsanis, N., Park, H. W., Leroux, M. R. (2010). Bardet-Biedl syndrome-associated small GTPase ARL6 (BBS3) functions at or near the ciliary gate and modulates Wnt signaling. J. Biol. Chem. 285, 16218-16230. Woo, K. and Fraser, S. E. (1995). Order and coherence in the fate map of the zebrafish nervous system. Development. 121, 2595-2609. Yamaguchi, M., Fujimori-Tonou, N., Yoshimura, Y., Kishi, T., Okamoto, H. and Masai, I. (2008). Mutation of DNA primase causes extensive apoptosis of retinal neurons through the activation of DNA damage checkpoint and tumor suppressor p53. Development. 135, 1247-1257. Yamaguchi, M., Tonou-Fujimori, N., Komori, A., Maeda, R., Nojima, Y., Li, H., Okamoto, H. and Masai, I. (2005). Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways. Development. 132, 3027-3043. Yamamoto, Y., Stock, D. W. and Jeffery, W. R. (2004). Hedgehog signalling controls eye degeneration in blind cavefish. Nature. 431, 844-847. Young, R.W. (1985). Cell differentiation in the retina of the mouse. Anat Rec. 212, 199-205. Zheng, L., Nancy, M. J., Stephen, S. and Easter, J. (2000). The morphogenesis of the zebrafish eye, including a fate map of the optic vesicle. Dev. Dyn. 218, 175-188. Zinszner, H., Kuroda, M., Wang, X., Batchvarova, N., Lightfoot, R. T., Remotti, H., Stevens, J. L. and Ron, D. (1998). CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12, 982-995. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22511 | - |
dc.description.abstract | 人類遺傳疾病巴德-畢德氏症候群第三型(Bardet-Biedl syndrome (BBS), type 3)被證實與ADP-ribosylation factor-like 6 (Arl6)突變有關,為求更加了解Arl6的功能,一些與Arl6交互作用的蛋白例如ADP-ribosylation factor-like 6 interacting protein 1 (Arl6ip1)、Sec61β、JWA等因此被發現。本文主要利用斑馬魚作為模式動物探討Arl6ip1在胚胎發育過程中所扮演的角色及功能。研究證實arl6ip1 mRNA於一細胞時期就能表現在blastodisc中,其均勻廣泛的表現可以持續至受精後24小時,之後漸漸地只會侷限在某些器官例如腦、眼、腎、心臟和鰭芽;顯微切片更詳細瞭解arl6ip1 mRNA在一些組織例如視網膜、hypochord、spinal cord、myotome也會表現,這些證據顯示Arl6ip1在胚胎發育過程中為一母體效應基因,並且有著動態性的表現分布;而當我們抑制Arl6ip1蛋白則發現上述這些器官或組織出現嚴重缺失例如扁平頭、小眼症、圍心腔腫大、色素異常表現、軀幹彎曲、tectum缺失、腎管發育不全、心管線性化、視網膜細胞不分化、不表現rod opsin和red cone opsin、失去視覺震顫能力且發育至第5天會死亡,這些喪失Arl6ip1的胚胎(arl6ip1-morphants)似乎與BBS病人具有部分相似病徵。為更進一步了解Arl6ip1的功能,我們先著重在上述最明顯易見的小眼症缺陷來探討Arl6ip1在retinogenesis之分子機制。首先我們觀察眼睛特化因子rx1和pax6的表現,證實兩因子並無受到太大影響;但在視網膜分化因子的表現則是嚴重缺失的,同時細胞移植實驗證明Arl6ip1以一non-cell autonomous的行為影響視網膜細胞的分化。為瞭解arl6ip1-morphants視網膜細胞分化是如何受到影響,我們先以視網膜切片計數arl6ip1-morphants的細胞數,結果顯示arl6ip1-morphants視網膜細胞數只有野生型的25%,利用TUNEL或FACS則證實視網膜細胞數少的原因是受到異常細胞週期而非過多細胞凋亡所致。Bromodeoxyuridine (BrdU)和phospho-histone H3 (PH3)更證實arl6ip1-morphants視網膜細胞有細胞週期延遲、大量活躍於S-phase和異常停留在M-phase的現象,由於這些異常的特徵與斑馬魚shh突變型之視網膜缺陷非常相似,因此我們想要利用Tg(shh:GFP)之轉殖品系追蹤胚胎缺失Arl6ip1時是否會影響Shh表現,結果顯示Tg(shh:GFP)缺失Arl6ip1後,在視網膜中觀察不到GFP表現;且Shh下游調控分子p57kip2也不表現,而p57kip2相對立因子cyclinD1則持續的表現於視網膜中,但若加以誘導表現p57kip2則能有效降低異常BrdU表現量,達到拯救因缺乏p57kip2所引起不正常細胞週期的缺陷,這些結果顯示Arl6ip1可能對Shh signaling pathway產生影響進而干擾視網膜細胞週期進行。另一方面,我們也觀察到arl6ip1-morphants視網膜細胞出現膨脹的內質網和高基氏體、形狀變異之粒線體、較大的細胞核以及chop mRNA高度表現,同時也觀察到細胞凋亡的現象出現在發育晚期的胚胎,這些證據顯示胚胎缺失Arl6ip1後可能會引起與內質網壓力有關的細胞凋亡。我們更進一步發現Arl6ip1與Ras-related nuclear protein (Ran)具有直接的交互作用,兩者共同座落於中心體,且在胚胎發育過程中的表現或缺失型態是相似的,尤其在ran-morphants視網膜也出現細胞不分化的現象,因此,我們推測Arl6ip1也可能藉由與Ran之交互作用共同去調節視網膜細胞週期的進行。總結,在胚胎發育過程中arl6ip1基因對斑馬魚胚胎的存活是必需的,且Arl6ip1更是扮演著多功能的角色影響視網膜的細胞增生、分化和存活。 | zh_TW |
dc.description.abstract | ADP-ribosylation factor-like 6 (Arl6) mutation is linked to human disease and that Arl6 interacts with Arl6 interacting protein 1 (Arl6ip1). However, the expression pattern and function of Arl6ip1 during embryogenesis are unknown. To confirm whether abnormal Arl6ip1 function might result in embryonic defects in zebrafish, we examined the expression patterns of arl6ip1 during embryogenesis, and we found that they were maternally expressed and exhibited in the brain, optic primordia, hypochord, spinal cord, myotome, heart, fin-bud, kidney, trunk and retina. Knockdown of Arl6ip1 revealed the following phenotypic defects: microphthalmia, disorganized pigment pattern, flat head, defective tectum, deficient pectoral fins, abnormal pneumatic duct, pericardial edema and deformed trunk. Particularly, histological dissection of the retinae of arl6ip1-morphants revealed defective retinal neurons and disorganized retinal layers. We further confirmed that opsins of arl6ip1-morphants were not transcribed. Based on these evidences, we propose that Arl6ip1 may play important roles in zebrafish ocular, heart and fin-bud development. Next, we focused on the retinal development to discuss the functional role(s) of Arl6ip1 that because small eyes were easily observed in all phenotypic defects. We demonstrated that Arl6ip1 is required for retinal differentiation in a non-cell autonomous manner. Arl6ip1-knockdown inhibits shh expression to block retinal cell differentiation and that loss of Arl6ip1 in embryos leads to defects in retinal cell cycle progression. Unlike the expression patterns of cyclinD1 and p57kip2 in wild-type embryos, arl6ip1-morphants keep cyclinD1 expression throughout the retina, and an undetectable p57kip2, suggesting that the retinal cells of arl6ip1-morphants proliferate abnormally, do not differentiate, and maintain in M-phase. Arl6ip1 maintains the integrity of organelles and the survival of retinal cells in that loss of Arl6ip1 function leads to ER-stress-mediated apoptosis at late developmental stage. We identified that Arl6ip1 binds to Ras-related nuclear protein (Ran) through cell cycle at centrosomes. The phenotypes of ran-morphants were similar to those of arl6ip1-morphants, suggesting that Arl6ip1 interacts with Ran to modulate cell cycle progression during retinogenesis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:19:33Z (GMT). No. of bitstreams: 1 ntu-99-D93b43001-1.pdf: 4619749 bytes, checksum: d24c8a44a7528bf7c77d8bec330d25ab (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 摘要 1
Abstract 4 文獻回顧 6 巴德-畢德氏症候群(Bardet-Biedl syndrome, BBS)的相關報告 6 Arl6的相關研究 7 ADP-ribosylation factor-like 6 interacting protein 1 (Arl6ip1)的相關研究 7 利用斑馬魚作為模式動物之優勢 8 斑馬魚視網膜的構造與發育相關基因之研究 9 序論 13 Chapter 1 The Embryonic Expression Patterns and the Knockdown Phenotypes of Zebrafish ADP-Ribosylation Factor-like 6 Interacting Protein 1 Gene Introduction 14 Materials and methods 17 Results and discussion 21 Chapter 2 Arl6ip1 Functions in Cell Differentiation, Proliferation and Survival during Retinogenesis of Zebrafish Embryos Introduction 30 Materials and methods 32 Results 39 Discussion 52 總論 57 References 58 Figures 66 Table 94 Movie 96 Curriculum Vitae 98 Publications 101 | |
dc.language.iso | en | |
dc.title | arl6ip1基因在斑馬魚胚胎的時空表現及其在視網膜發育過程之功能 | zh_TW |
dc.title | Spatiotemporal Expressions during Embryogenesis and Functional Roles during Retinogenesis of Zebrafish arl6ip1 Gene | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 楊長豪,孫以瀚,董桂書,王致恬 | |
dc.subject.keyword | 斑馬魚,視網膜,細胞分化,細胞增生,細胞凋亡,細胞週期, | zh_TW |
dc.subject.keyword | Arl6ip1,zebrafish,retina,cell proliferation,cell differentiation,apoptosis,cell cycle, | en |
dc.relation.page | 101 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2010-07-22 | |
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-99-1.pdf 目前未授權公開取用 | 4.51 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。