請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19869完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃憲松 | |
| dc.contributor.author | Shih-Chuan Huang | en |
| dc.contributor.author | 黃士荃 | zh_TW |
| dc.date.accessioned | 2021-06-08T02:24:09Z | - |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-18 | |
| dc.identifier.citation | 1. McGrath, J. Solter, D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37, 179-183 (1984). 2. Reik, W. Walter, J. Genomic imprinting: parental influence on the genome. Nature reviews. Genetics 2, 21-32 (2001). 3. Wilkinson, L.S., Davies, W. Isles, A.R. Genomic imprinting effects on brain development and function. Nature reviews. Neuroscience 8, 832-843 (2007). 4. Moore, T. Haig, D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends in genetics : TIG 7, 45-49 (1991). 5. DeChiara, T.M., Robertson, E.J. Efstratiadis, A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, 849-859 (1991). 6. Barlow, D.P., Stoger, R., Herrmann, B.G., Saito, K. Schweifer, N. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349, 84-87 (1991). 7. Allen, N.D., et al. Distribution of parthenogenetic cells in the mouse brain and their influence on brain development and behavior. Proceedings of the National Academy of Sciences of the United States of America 92, 10782-10786 (1995). 8. Davies, W., Isles, A.R. Wilkinson, L.S. Imprinted gene expression in the brain. Neuroscience and biobehavioral reviews 29, 421-430 (2005). 9. Buiting, K. Prader-Willi syndrome and Angelman syndrome. American journal of medical genetics. Part C, Seminars in medical genetics 154C, 365-376 (2010). 10. Huang, H.S., et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481, 185-189 (2012). 11. Judson, M.C., Sosa-Pagan, J.O., Del Cid, W.A., Han, J.E. Philpot, B.D. Allelic specificity of Ube3a expression in the mouse brain during postnatal development. The Journal of comparative neurology 522, 1874-1896 (2014). 12. Pham, N.V., Nguyen, M.T., Hu, J.F., Vu, T.H. Hoffman, A.R. Dissociation of IGF2 and H19 imprinting in human brain. Brain research 810, 1-8 (1998). 13. Wang, Y., et al. The mouse Murr1 gene is imprinted in the adult brain, presumably due to transcriptional interference by the antisense-oriented U2af1-rs1 gene. Molecular and cellular biology 24, 270-279 (2004). 14. Levelt, C.N. Hubener, M. Critical-period plasticity in the visual cortex. Annual review of neuroscience 35, 309-330 (2012). 15. Mower, G.D. The effect of dark rearing on the time course of the critical period in cat visual cortex. Brain research. Developmental brain research 58, 151-158 (1991). 16. Gordon, J.A. Stryker, M.P. Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse. The Journal of neuroscience : the official journal of the Society for Neuroscience 16, 3274-3286 (1996). 17. Iwai, Y., Fagiolini, M., Obata, K. Hensch, T.K. Rapid critical period induction by tonic inhibition in visual cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 23, 6695-6702 (2003). 18. Reppert, S.M. Weaver, D.R. Molecular analysis of mammalian circadian rhythms. Annual review of physiology 63, 647-676 (2001). 19. Masri, S. Sassone-Corsi, P. Plasticity and specificity of the circadian epigenome. Nature neuroscience 13, 1324-1329 (2010). 20. Bechtold, D.A., Gibbs, J.E. Loudon, A.S. Circadian dysfunction in disease. Trends in pharmacological sciences 31, 191-198 (2010). 21. Ren, J.Q., Aika, Y., Heizmann, C.W. Kosaka, T. Quantitative analysis of neurons and glial cells in the rat somatosensory cortex, with special reference to GABAergic neurons and parvalbumin-containing neurons. Experimental brain research 92, 1-14 (1992). 22. Dori, I.E., Dinopoulos, A. Parnavelas, J.G. The development of the synaptic organization of the serotonergic system differs in brain areas with different functions. Experimental neurology 154, 113-125 (1998). 23. White, E.L. (ed.) Cortical Circuits. Synaptic Organization of the Cerebral Cortex (Birkhauser, Boston, 1989). 24. Letinic, K., Zoncu, R. Rakic, P. Origin of GABAergic neurons in the human neocortex. Nature 417, 645-649 (2002). 25. Owens, D.F. Kriegstein, A.R. Is there more to GABA than synaptic inhibition? Nature reviews. Neuroscience 3, 715-727 (2002). 26. Morales, B., Choi, S.Y. Kirkwood, A. Dark rearing alters the development of GABAergic transmission in visual cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 22, 8084-8090 (2002). 27. Chen, L., Yang, C. Mower, G.D. Developmental changes in the expression of GABA(A) receptor subunits (alpha(1), alpha(2), alpha(3)) in the cat visual cortex and the effects of dark rearing. Brain research. Molecular brain research 88, 135-143 (2001). 28. Fagiolini, M. Hensch, T.K. Inhibitory threshold for critical-period activation in primary visual cortex. Nature 404, 183-186 (2000). 29. Marin, O. Interneuron dysfunction in psychiatric disorders. Nature reviews. Neuroscience 13, 107-120 (2012). 30. Homanics, G.E., et al. Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proceedings of the National Academy of Sciences of the United States of America 94, 4143-4148 (1997). 31. Egawa, K., et al. Aberrant somatosensory-evoked responses imply GABAergic dysfunction in Angelman syndrome. NeuroImage 39, 593-599 (2008). 32. Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233 (2009). 33. Friedman, R.C., Farh, K.K., Burge, C.B. Bartel, D.P. Most mammalian mRNAs are conserved targets of microRNAs. Genome research 19, 92-105 (2009). 34. Krichevsky, A.M., King, K.S., Donahue, C.P., Khrapko, K. Kosik, K.S. A microRNA array reveals extensive regulation of microRNAs during brain development. Rna 9, 1274-1281 (2003). 35. Miska, E.A., et al. Microarray analysis of microRNA expression in the developing mammalian brain. Genome biology 5, R68 (2004). 36. Sempere, L.F., et al. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome biology 5, R13 (2004). 37. Kim, J., et al. Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proceedings of the National Academy of Sciences of the United States of America 101, 360-365 (2004). 38. Lagos-Quintana, M., et al. Identification of tissue-specific microRNAs from mouse. Current biology : CB 12, 735-739 (2002). 39. Schratt, G.M., et al. A brain-specific microRNA regulates dendritic spine development. Nature 439, 283-289 (2006). 40. Issler, O. Chen, A. Determining the role of microRNAs in psychiatric disorders. Nature reviews. Neuroscience 16, 201-212 (2015). 41. Griggs, E.M., Young, E.J., Rumbaugh, G. Miller, C.A. MicroRNA-182 regulates amygdala-dependent memory formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 33, 1734-1740 (2013). 42. Im, H.I., Hollander, J.A., Bali, P. Kenny, P.J. MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nature neuroscience 13, 1120-1127 (2010). 43. Borchert, G.M., Lanier, W. Davidson, B.L. RNA polymerase III transcribes human microRNAs. Nature structural molecular biology 13, 1097-1101 (2006). 44. Lee, Y., et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415-419 (2003). 45. Chendrimada, T.P., et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436, 740-744 (2005). 46. Hausser, J. Zavolan, M. Identification and consequences of miRNA-target interactions--beyond repression of gene expression. Nature reviews. Genetics 15, 599-612 (2014). 47. Cavaille, J., et al. Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proceedings of the National Academy of Sciences of the United States of America 97, 14311-14316 (2000). 48. Meguro, M., et al. Large-scale evaluation of imprinting status in the Prader-Willi syndrome region: an imprinted direct repeat cluster resembling small nucleolar RNA genes. Human molecular genetics 10, 383-394 (2001). 49. Seitz, H., et al. A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome research 14, 1741-1748 (2004). 50. Seitz, H., et al. Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nature genetics 34, 261-262 (2003). 51. Nomura, T., et al. MeCP2-dependent repression of an imprinted miR-184 released by depolarization. Human molecular genetics 17, 1192-1199 (2008). 52. Liu, C., et al. Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell stem cell 6, 433-444 (2010). 53. Jiang, Y., Matevossian, A., Huang, H.S., Straubhaar, J. Akbarian, S. Isolation of neuronal chromatin from brain tissue. BMC neuroscience 9, 42 (2008). 54. Esclapez, M., Tillakaratne, N.J., Kaufman, D.L., Tobin, A.J. Houser, C.R. Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms. The Journal of neuroscience : the official journal of the Society for Neuroscience 14, 1834-1855 (1994). 55. Majdan, M. Shatz, C.J. Effects of visual experience on activity-dependent gene regulation in cortex. Nature neuroscience 9, 650-659 (2006). 56. Desai, N.S., Cudmore, R.H., Nelson, S.B. Turrigiano, G.G. Critical periods for experience-dependent synaptic scaling in visual cortex. Nature neuroscience 5, 783-789 (2002). 57. Su, H., Trombly, M.I., Chen, J. Wang, X. Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Genes development 23, 304-317 (2009). 58. Liao, J., Liu, R., Yin, L. Pu, Y. Expression profiling of exosomal miRNAs derived from human esophageal cancer cells by Solexa high-throughput sequencing. International journal of molecular sciences 15, 15530-15551 (2014). 59. Kobayashi, S., et al. Identification of an imprinted gene cluster in the X-inactivation center. PloS one 8, e71222 (2013). 60. Mellios, N., et al. miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity. Nature neuroscience 14, 1240-1242 (2011). 61. Kishino, T., Lalande, M. Wagstaff, J. UBE3A/E6-AP mutations cause Angelman syndrome. Nature genetics 15, 70-73 (1997). 62. Yamasaki, K., et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Human molecular genetics 12, 837-847 (2003). 63. Remedios, R., Subramanian, L. Tole, S. LIM genes parcellate the embryonic amygdala and regulate its development. The Journal of neuroscience : the official journal of the Society for Neuroscience 24, 6986-6990 (2004). 64. Schaefer, A., et al. Argonaute 2 in dopamine 2 receptor-expressing neurons regulates cocaine addiction. The Journal of experimental medicine 207, 1843-1851 (2010). 65. Liu, J., et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437-1441 (2004). 66. Muddashetty, R.S., et al. Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Molecular cell 42, 673-688 (2011). 67. Huang, H.S., et al. Snx14 regulates neuronal excitability, promotes synaptic transmission, and is imprinted in the brain of mice. PloS one 9, e98383 (2014). 68. Ma, L., et al. Zac1 functions through TGFbetaII to negatively regulate cell number in the developing retina. Neural development 2, 11 (2007). 69. Varrault, A., et al. Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Developmental cell 11, 711-722 (2006). 70. Maebayashi, Y., Shigeyoshi, Y., Takumi, T. Okamura, H. A putative transcription factor with seven zinc-finger motifs identified in the developing suprachiasmatic nucleus by the differential display PCR method. The Journal of neuroscience : the official journal of the Society for Neuroscience 19, 10176-10183 (1999). 71. Fu, Y., Dominissini, D., Rechavi, G. He, C. Gene expression regulation mediated through reversible m(6)A RNA methylation. Nature reviews. Genetics 15, 293-306 (2014). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19869 | - |
| dc.description.abstract | 基因體印記（genomic imprinting）是被歸類在表觀遺傳學（Epigenetics）裡的現象，主要是藉由甲基化的修飾，造成基因的表現會受父方或母方來源的等位基因 (allele)來影響。此現象主要發生在腦部，而且異常的印記基因（imprinted gene）與許多神經疾病有關。由此看來，基因體印記在腦部扮演著重要的角色，但並沒有一個全面性的研究，可以讓我們深入地了解其中的關連。因此在我們的研究中，中心目標是探討基因體印記在不同細胞型態、生長發育階段及環境條件的表現。此三種因素在之前的研究中，被發現可能會影響基因體印記的狀態。我們調控光線的有無來製造不同環境，發現許多印記基因在視網膜（retina）、視叉上核（Suprachiasmatic nucleus）、視覺皮層（visual cortex） （統稱為視覺系統）發生變化；其中我們發現一個負責調控微小核糖核酸（imprinted microRNA）的基因-Ago2可能是只有在腦部才會發生印記的情形。我們也觀察到可能是興奮性神經元、抑制性神經元、或星狀膠細胞特有的印記基因。另外，我們也對印記微小核糖核酸有興趣，因為之前的研究中發現有調控印記基因的功能。為了要研究此類微小核醣核酸的功能，我們建立了可以測量其表現量的系統。雖然此研究包含許多部份，但都圍繞在”基因體印記”這個主題。我們期許這樣廣泛性的研究可以了解印記基因在腦中的變化情形以及所扮演的角色。 | zh_TW |
| dc.description.abstract | Genomic imprinting refers to an epigenetic mark that distinguishes parental alleles and results in a monoallelic, parent-of-origin-specific expression pattern in mammals. Genomic imprinting occurs in the brain and dysfunctional imprinted genes cause various neurological and psychiatric disorders. Despite the important roles of genomic imprinting, the physiological roles of imprinted genes in the brain are still limited. To fully understand imprinted genes in brain, factors that may influence genomic imprinting status were considered in our study. Accordingly, our aim was to profile three dimensions of imprinting status in the brain: different cell types, developmental stages, and environmental condition. We used dark rearing system to manipulate environmental factors, and observed dynamic imprinted genes in visual system, including the retina, the suprachiasmatic nucleus (SCN), and the visual cortex (VC). Among of the imprinted genes, we are interested in Ago2 that was found to be a brain-specific imprinted gene. We also observed genes may be specifically imprinted in excitatory neurons, interneurons, or astrocytes. Additionally, we profiled imprinted miRNAs, which are able to regulate imprinted genes. To investigate miRNA function, a special quantification system was built. This study contains many parts, but they are all surrounding the subject “genomic imprinting”. We hope our study may enable us to learn more about the function and roles of genomic imprinting in the brain. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T02:24:09Z (GMT). No. of bitstreams: 1 ntu-104-R02454003-1.pdf: 8602081 bytes, checksum: 7c61de5a57d821819721eaace9b1c51f (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員會審定書 ii Acknowledgement iii 中文摘要 iv Abstract v 目錄 iii 圖目錄 ix 表目錄 x Chapter 1: Introduction 1 1.1 What is genomic imprinting? 1 1.2 Visual system: retina, suprachiasmatic nucleus, and visual cortex 3 1.3 Specific cell type: interneuron 5 1.4 Aim of the comprehensive study: Profiling three dimensional genomic imprinting statuses in the visual system 6 1.5 Imprinted miRNA 7 1.5.1 miRNA biosynthesis 7 1.5.2 Imprinted miRNA 8 Chapter 2: Material and methods 9 2.1 Mice 9 2.2 Immunofluorescence staining 10 2.3 LCM: single cell type isolation 11 2.4 LCM: Interneuron RNA isolation, library preparation and sequencing 11 2.5 RNA-Seq analysis 12 2.6 FACS: single cell type isolation and RNA extraction 12 2.7 Tissue RNA extraction 13 2.8 cDNA conversion and PCR 13 2.9 Sanger sequencing 14 2.10 Real-time qPCR analysis 14 2.11 miRNA quantification 14 2.12 Statistical analysis 15 Chapter 3: Results 16 3.1 The Cre/loxP recombination system mediates expression of red florescent signal in interneuron 16 3.2 RNA sequencing data of dynamic imprinted genes 16 3.2.1 Validation of dark rearing system 17 3.2.2 LCM-collected interneurons from layer 2/3 of the visual cortex (P28) 17 3.2.3 Experience- regulated genomic imprinting in the brain (P28) 18 3.2.4 Sanger sequencing confirmation of imprinted genes 20 3.2.5 Ago2 imprinting status 21 3.3 Interneuron collection by FACS 22 3.4 Comprehensively profiling imprinted miRNA 23 3.4.1 Small RNA sequencing of mouse visual cortex (P28) 23 3.4.2 miRNA quantification 24 3.4.3 Imprinting status of mir-125b-2 25 Chapter 4: Discussion 27 4.1 Summary and interpretation of the results 27 4.2 limitation of our study 31 Reference 78 | |
| dc.language.iso | en | |
| dc.title | 探索小鼠視覺皮質層中抑制性神經元的印記體 | zh_TW |
| dc.title | Determination of Dynamic Imprintome in the Interneuron of Mouse Visual Cortex | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 阮麗蓉,俞松良,莊樹諄 | |
| dc.subject.keyword | 基因體印記,視覺系統,抑制性神經元,Ago2,微小核糖核酸?, | zh_TW |
| dc.subject.keyword | genomic imprinting,visual system,interneuron,Ago2,miRNA, | en |
| dc.relation.page | 85 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2015-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 腦與心智科學研究所 | zh_TW |
| 顯示於系所單位： | 腦與心智科學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-104-1.pdf 目前未授權公開取用 | 8.4 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。