Please use this identifier to cite or link to this item:
Full metadata record
|dc.identifier.citation||1. McGrath, J. and D. Solter, Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell, 1984. 37(1): p. 179-83.
2. Barton, S.C., M.A. Surani, and M.L. Norris, Role of paternal and maternal genomes in mouse development. Nature, 1984. 311(5984): p. 374-6.
3. Lawson, H.A., J.M. Cheverud, and J.B. Wolf, Genomic imprinting and parent-of-origin effects on complex traits. Nat Rev Genet, 2013. 14(9): p. 609-17.
4. Moore, T. and D. Haig, Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet, 1991. 7(2): p. 45-9.
5. DeChiara, T.M., E.J. Robertson, and A. Efstratiadis, Parental imprinting of the mouse insulin-like growth factor II gene. Cell, 1991. 64(4): p. 849-59.
6. Barlow, D.P., et al., The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature, 1991. 349(6304): p. 84-7.
7. Meaney, M.J. and A.C. Ferguson-Smith, Epigenetic regulation of the neural transcriptome: the meaning of the marks. Nat Neurosci, 2010. 13(11): p. 1313-8.
8. Martienssen, R.A. and V. Colot, DNA methylation and epigenetic inheritance in plants and filamentous fungi. Science, 2001. 293(5532): p. 1070-4.
9. Feil, R. and F. Berger, Convergent evolution of genomic imprinting in plants and mammals. Trends Genet, 2007. 23(4): p. 192-9.
10. Wilkins, J.F., F. Ubeda, and J. Van Cleve, The evolving landscape of imprinted genes in humans and mice: Conflict among alleles, genes, tissues, and kin. Bioessays, 2016. 38(5): p. 482-9.
11. Babak, T., et al., Genetic conflict reflected in tissue-specific maps of genomic imprinting in human and mouse. Nat Genet, 2015. 47(5): p. 544-9.
12. Baran, Y., et al., The landscape of genomic imprinting across diverse adult human tissues. Genome Res, 2015. 25(7): p. 927-36.
13. Crowley, J.J., et al., Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance. Nat Genet, 2015. 47(4): p. 353-60.
14. Wilkinson, L.S., W. Davies, and A.R. Isles, Genomic imprinting effects on brain development and function. Nat Rev Neurosci, 2007. 8(11): p. 832-43.
15. Davies, W., A.R. Isles, and L.S. Wilkinson, Imprinted gene expression in the brain. Neurosci Biobehav Rev, 2005. 29(3): p. 421-30.
16. Isles, A.R. and L.S. Wilkinson, Imprinted genes, cognition and behaviour. Trends Cogn Sci, 2000. 4(8): p. 309-318.
17. Ferron, S.R., et al., Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis. Nature, 2011. 475(7356): p. 381-5.
18. Schmidt-Edelkraut, U., et al., Zac1 regulates astroglial differentiation of neural stem cells through Socs3. Stem Cells, 2013. 31(8): p. 1621-32.
19. Mardirossian, S., et al., Impaired hippocampal plasticity and altered neurogenesis in adult Ube3a maternal deficient mouse model for Angelman syndrome. Exp Neurol, 2009. 220(2): p. 341-8.
20. Sato, M. and M.P. Stryker, Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a. Proc Natl Acad Sci U S A, 2010. 107(12): p. 5611-6.
21. Wallace, M.L., et al., Maternal loss of Ube3a produces an excitatory/inhibitory imbalance through neuron type-specific synaptic defects. Neuron, 2012. 74(5): p. 793-800.
22. Yashiro, K., et al., Ube3a is required for experience-dependent maturation of the neocortex. Nat Neurosci, 2009. 12(6): p. 777-83.
23. Huang, H.S., et al., Snx14 regulates neuronal excitability, promotes synaptic transmission, and is imprinted in the brain of mice. PLoS One, 2014. 9(5): p. e98383.
24. Schaaf, C.P., et al., Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat Genet, 2013. 45(11): p. 1405-8.
25. Cook, E.H., Jr., et al., Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet, 1997. 60(4): p. 928-34.
26. Kishino, T., M. Lalande, and J. Wagstaff, UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet, 1997. 15(1): p. 70-3.
27. Matsuura, T., et al., De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet, 1997. 15(1): p. 74-7.
28. Sahoo, T., et al., Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet, 2008. 40(6): p. 719-21.
29. Horike, S., et al., Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet, 2005. 37(1): p. 31-40.
30. Skuse, D.H., et al., Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function. Nature, 1997. 387(6634): p. 705-8.
31. Plagge, A., et al., Imprinted Nesp55 influences behavioral reactivity to novel environments. Mol Cell Biol, 2005. 25(8): p. 3019-26.
32. Runte, M., et al., SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome. Hum Genet, 2004. 114(6): p. 553-61.
33. Aizawa, T., et al., Expression of necdin, an embryonal carcinoma-derived nuclear protein, in developing mouse brain. Brain Res Dev Brain Res, 1992. 68(2): p. 265-74.
34. McLaughlin, D., et al., Expression pattern of the maternally imprinted gene Gtl2 in the forebrain during embryonic development and adulthood. Gene Expr Patterns, 2006. 6(4): p. 394-9.
35. Pham, N.V., et al., Dissociation of IGF2 and H19 imprinting in human brain. Brain Res, 1998. 810(1-2): p. 1-8.
36. 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. Mol Cell Biol, 2004. 24(1): p. 270-9.
37. Zhang, Z., et al., Comparative analyses of genomic imprinting and CpG island-methylation in mouse Murr1 and human MURR1 loci revealed a putative imprinting control region in mice. Gene, 2006. 366(1): p. 77-86.
38. Okita, C., et al., A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids. Genomics, 2003. 81(6): p. 556-9.
39. Kimura, M.I., et al., Dlx5, the mouse homologue of the human-imprinted DLX5 gene, is biallelically expressed in the mouse brain. J Hum Genet, 2004. 49(5): p. 273-7.
40. Albrecht, U., et al., Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat Genet, 1997. 17(1): p. 75-8.
41. Yamasaki, K., et al., Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum Mol Genet, 2003. 12(8): p. 837-47.
42. Huang, H.S., et al., Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature, 2012. 481(7380): p. 185-9.
43. Reynolds, B.A., W. Tetzlaff, and S. Weiss, A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci, 1992. 12(11): p. 4565-74.
44. Reynolds, B.A. and S. Weiss, Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 1992. 255(5052): p. 1707-10.
45. Gotz, M. and W.B. Huttner, The cell biology of neurogenesis. Nat Rev Mol Cell Biol, 2005. 6(10): p. 777-88.
46. Gotz, M. and Y.A. Barde, Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons. Neuron, 2005. 46(3): p. 369-72.
47. Ming, G.L. and H. Song, Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron, 2011. 70(4): p. 687-702.
48. Paridaen, J.T. and W.B. Huttner, Neurogenesis during development of the vertebrate central nervous system. EMBO Rep, 2014. 15(4): p. 351-64.
49. Rowitch, D.H. and A.R. Kriegstein, Developmental genetics of vertebrate glial-cell specification. Nature, 2010. 468(7321): p. 214-22.
50. Gallo, V. and B. Deneen, Glial development: the crossroads of regeneration and repair in the CNS. Neuron, 2014. 83(2): p. 283-308.
51. Doetsch, F., et al., Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell, 1999. 97(6): p. 703-16.
52. Stolp, H.B. and Z. Molnar, Neurogenic niches in the brain: help and hindrance of the barrier systems. Front Neurosci, 2015. 9: p. 20.
53. Alvarez-Buylla, A. and D.A. Lim, For the long run: maintaining germinal niches in the adult brain. Neuron, 2004. 41(5): p. 683-6.
54. Ma, D.K., G.L. Ming, and H. Song, Glial influences on neural stem cell development: cellular niches for adult neurogenesis. Curr Opin Neurobiol, 2005. 15(5): p. 514-20.
55. Mu, Y. and F.H. Gage, Adult hippocampal neurogenesis and its role in Alzheimer's disease. Mol Neurodegener, 2011. 6: p. 85.
56. Desplats, P., et al., alpha-Synuclein induces alterations in adult neurogenesis in Parkinson disease models via p53-mediated repression of Notch1. J Biol Chem, 2012. 287(38): p. 31691-702.
57. Kim, J.Y., et al., DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron, 2009. 63(6): p. 761-73.
58. Kim, J.Y., et al., Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia. Cell, 2012. 148(5): p. 1051-64.
59. Meechan, D.W., et al., Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci U S A, 2009. 106(38): p. 16434-45.
60. Genovesi, L.A., et al., Integrated analysis of miRNA and mRNA expression in childhood medulloblastoma compared with neural stem cells. PLoS One, 2011. 6(9): p. e23935.
61. Ladran, I., et al., Neural stem and progenitor cells in health and disease. Wiley Interdiscip Rev Syst Biol Med, 2013. 5(6): p. 701-15.
62. Ferron, S.R., et al., Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. Nat Commun, 2015. 6: p. 8265.
63. Takashima, Y., et al., Neuroepithelial cells supply an initial transient wave of MSC differentiation. Cell, 2007. 129(7): p. 1377-88.
64. Casanova, E., et al., A CamKIIalpha iCre BAC allows brain-specific gene inactivation. Genesis, 2001. 31(1): p. 37-42.
65. Pevny, L.H., et al., A role for SOX1 in neural determination. Development, 1998. 125(10): p. 1967-78.
66. Zhao, S., et al., SoxB transcription factors specify neuroectodermal lineage choice in ES cells. Mol Cell Neurosci, 2004. 27(3): p. 332-42.
67. Favaro, R., et al., Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci, 2009. 12(10): p. 1248-56.
68. Sibbe, M., et al., Experimental epilepsy affects Notch1 signalling and the stem cell pool in the dentate gyrus. Eur J Neurosci, 2012. 36(12): p. 3643-52.
69. Ehm, O., et al., RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. J Neurosci, 2010. 30(41): p. 13794-807.
70. Mullen, R.J., C.R. Buck, and A.M. Smith, NeuN, a neuronal specific nuclear protein in vertebrates. Development, 1992. 116(1): p. 201-11.
71. Wolf, H.K., et al., NeuN: a useful neuronal marker for diagnostic histopathology. J Histochem Cytochem, 1996. 44(10): p. 1167-71.
72. Huang, G.J., et al., Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice. PLoS One, 2014. 9(2): p. e86471.
73. Matsuo-Takasaki, M., et al., Cloning and expression of a novel zinc finger gene, Fez, transcribed in the forebrain of Xenopus and mouse embryos. Mech Dev, 2000. 93(1-2): p. 201-4.
74. Chen, B., L.R. Schaevitz, and S.K. McConnell, Fezl regulates the differentiation and axon targeting of layer 5 subcortical projection neurons in cerebral cortex. Proc Natl Acad Sci U S A, 2005. 102(47): p. 17184-9.
75. Berberoglu, M.A., et al., Heterogeneously expressed fezf2 patterns gradient Notch activity in balancing the quiescence, proliferation, and differentiation of adult neural stem cells. J Neurosci, 2014. 34(42): p. 13911-23.
76. Kwan, K.Y., et al., SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons. Proc Natl Acad Sci U S A, 2008. 105(41): p. 16021-6.
77. Bouschet, T., et al., In Vitro Corticogenesis from Embryonic Stem Cells Recapitulates the In Vivo Epigenetic Control of Imprinted Gene Expression. Cereb Cortex, 2016.
78. DeVeale, B., D. van der Kooy, and T. Babak, Critical evaluation of imprinted gene expression by RNA-Seq: a new perspective. PLoS Genet, 2012. 8(3): p. e1002600.
79. Okae, H., et al., Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression. Hum Mol Genet, 2012. 21(3): p. 548-58.
80. Ko, Y., et al., Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain. Proc Natl Acad Sci U S A, 2013. 110(8): p. 3095-100.
81. Morison, I.M., J.P. Ramsay, and H.G. Spencer, A census of mammalian imprinting. Trends Genet, 2005. 21(8): p. 457-65.
82. Nikaido, I., et al., Discovery of imprinted transcripts in the mouse transcriptome using large-scale expression profiling. Genome Res, 2003. 13(6B): p. 1402-9.
83. Ruf, N., et al., Expression profiling of uniparental mouse embryos is inefficient in identifying novel imprinted genes. Genomics, 2006. 87(4): p. 509-19.
84. Babak, T., et al., Global survey of genomic imprinting by transcriptome sequencing. Curr Biol, 2008. 18(22): p. 1735-41.
85. Gregg, C., et al., High-resolution analysis of parent-of-origin allelic expression in the mouse brain. Science, 2010. 329(5992): p. 643-8.
86. Takahashi, T. and T. Nakayama, Novel technique of quantitative nested real-time PCR assay for Mycobacterium tuberculosis DNA. J Clin Microbiol, 2006. 44(3): p. 1029-39.
87. Hueston, L., et al., Diagnosis of Barmah Forest virus infection by a nested real-time SYBR green RT-PCR assay. PLoS One, 2013. 8(7): p. e65197.
88. Barr, M.L. and E.G. Bertram, A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature, 1949. 163(4148): p. 676.
89. Ohno, S., W.D. Kaplan, and R. Kinosita, Formation of the sex chromatin by a single X-chromosome in liver cells of Rattus norvegicus. Exp Cell Res, 1959. 18: p. 415-8.
90. Zechner, U., et al., A high density of X-linked genes for general cognitive ability: a run-away process shaping human evolution? Trends Genet, 2001. 17(12): p. 697-701.
91. Halladay, A.K., et al., Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority. Mol Autism, 2015. 6: p. 36.
92. Rutter, M., et al., Sex differences in developmental reading disability: new findings from 4 epidemiological studies. JAMA, 2004. 291(16): p. 2007-12.
93. Baron-Cohen, S., The extreme male brain theory of autism. Trends Cogn Sci, 2002. 6(6): p. 248-254.
94. Hermens, D.F., et al., Sex differences in adult ADHD: a double dissociation in brain activity and autonomic arousal. Biol Psychol, 2004. 66(3): p. 221-33.
95. Lyon, M.F., Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature, 1961. 190: p. 372-3.
96. Chow, J.C., et al., Silencing of the mammalian X chromosome. Annu Rev Genomics Hum Genet, 2005. 6: p. 69-92.
97. Lee, J.T. and M.S. Bartolomei, X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell, 2013. 152(6): p. 1308-23.
98. Sharman, G.B., Late DNA replication in the paternally derived X chromosome of female kangaroos. Nature, 1971. 230(5291): p. 231-2.
99. Takagi, N. and M. Sasaki, Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature, 1975. 256(5519): p. 640-2.
100. Lifschytz, E. and D.L. Lindsley, The role of X-chromosome inactivation during spermatogenesis (Drosophila-allocycly-chromosome evolution-male sterility-dosage compensation). Proc Natl Acad Sci U S A, 1972. 69(1): p. 182-6.
101. Sun, S., et al., Xist imprinting is promoted by the hemizygous (unpaired) state in the male germ line. Proc Natl Acad Sci U S A, 2015. 112(47): p. 14415-22.
102. Namekawa, S.H., et al., Two-step imprinted X inactivation: repeat versus genic silencing in the mouse. Mol Cell Biol, 2010. 30(13): p. 3187-205.
103. Okamoto, I. and E. Heard, The dynamics of imprinted X inactivation during preimplantation development in mice. Cytogenet Genome Res, 2006. 113(1-4): p. 318-24.
104. Takagi, N. and K. Abe, Detrimental effects of two active X chromosomes on early mouse development. Development, 1990. 109(1): p. 189-201.
105. Goto, Y. and N. Takagi, Maternally inherited X chromosome is not inactivated in mouse blastocysts due to parental imprinting. Chromosome Res, 2000. 8(2): p. 101-9.
106. Davies, W., et al., X-linked imprinting: effects on brain and behaviour. Bioessays, 2006. 28(1): p. 35-44.
107. Davies, W., et al., Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice. Nat Genet, 2005. 37(6): p. 625-9.
108. Kobayashi, S., et al., The X-linked imprinted gene family Fthl17 shows predominantly female expression following the two-cell stage in mouse embryos. Nucleic Acids Res, 2010. 38(11): p. 3672-81.
109. Li, Y., P. Lemaire, and R.R. Behringer, Esx1, a novel X chromosome-linked homeobox gene expressed in mouse extraembryonic tissues and male germ cells. Dev Biol, 1997. 188(1): p. 85-95.
110. Lee, J.T., Disruption of imprinted X inactivation by parent-of-origin effects at Tsix. Cell, 2000. 103(1): p. 17-27.
111. Raefski, A.S. and M.J. O'Neill, Identification of a cluster of X-linked imprinted genes in mice. Nat Genet, 2005. 37(6): p. 620-4.
112. Thiselton, D.L., et al., An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. Genomics, 2002. 79(4): p. 560-72.
113. Carroll, J., et al., Definition of the nuclear encoded protein composition of bovine heart mitochondrial complex I. Identification of two new subunits. J Biol Chem, 2002. 277(52): p. 50311-7.
114. Mimaki, M., et al., Understanding mitochondrial complex I assembly in health and disease. Biochim Biophys Acta, 2012. 1817(6): p. 851-62.
115. Petruzzella, V., et al., The NDUFB11 gene is not a modifier in Leber hereditary optic neuropathy. Biochem Biophys Res Commun, 2007. 355(1): p. 181-7.
116. Gurok, U., et al., Expression of Ndufb11 encoding the neuronal protein 15.6 during neurite outgrowth and development. Gene Expr Patterns, 2007. 7(3): p. 370-4.
117. van Rahden, V.A., et al., Mutations in NDUFB11, encoding a complex I component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome. Am J Hum Genet, 2015. 96(4): p. 640-50.
118. Shehata, B.M., et al., Exome sequencing of patients with histiocytoid cardiomyopathy reveals a de novo NDUFB11 mutation that plays a role in the pathogenesis of histiocytoid cardiomyopathy. Am J Med Genet A, 2015. 167A(9): p. 2114-21.
119. Torraco, A., et al., A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia. Clin Genet, 2016.
120. Bonthuis, P.J., et al., Noncanonical Genomic Imprinting Effects in Offspring. Cell Rep, 2015. 12(6): p. 979-91.
121. Gregg, C., et al., Sex-specific parent-of-origin allelic expression in the mouse brain. Science, 2010. 329(5992): p. 682-5.
122. Kozlov, S.V., et al., The imprinted gene Magel2 regulates normal circadian output. Nat Genet, 2007. 39(10): p. 1266-72.
123. Levelt, C.N. and M. Hubener, Critical-period plasticity in the visual cortex. Annu Rev Neurosci, 2012. 35: p. 309-30.
124. Mower, G.D., The effect of dark rearing on the time course of the critical period in cat visual cortex. Brain Res Dev Brain Res, 1991. 58(2): p. 151-8.
125. Gordon, J.A. and M.P. Stryker, Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse. J Neurosci, 1996. 16(10): p. 3274-86.
126. Iwai, Y., et al., Rapid critical period induction by tonic inhibition in visual cortex. J Neurosci, 2003. 23(17): p. 6695-702.
127. Reppert, S.M. and D.R. Weaver, Molecular analysis of mammalian circadian rhythms. Annu Rev Physiol, 2001. 63: p. 647-76.
128. Masri, S. and P. Sassone-Corsi, Plasticity and specificity of the circadian epigenome. Nat Neurosci, 2010. 13(11): p. 1324-9.
129. Bechtold, D.A., J.E. Gibbs, and A.S. Loudon, Circadian dysfunction in disease. Trends Pharmacol Sci, 2010. 31(5): p. 191-8.
130. Gall, J.G. and M.L. Pardue, Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci U S A, 1969. 63(2): p. 378-83.
131. Pardue, M.L. and J.G. Gall, Molecular hybridization of radioactive DNA to the DNA of cytological preparations. Proc Natl Acad Sci U S A, 1969. 64(2): p. 600-4.
132. Langer-Safer, P.R., M. Levine, and D.C. Ward, Immunological method for mapping genes on Drosophila polytene chromosomes. Proc Natl Acad Sci U S A, 1982. 79(14): p. 4381-5.
133. Raj, A., et al., Imaging individual mRNA molecules using multiple singly labeled probes. Nat Methods, 2008. 5(10): p. 877-9.
134. Brown, J.M. and V.J. Buckle, Detection of nascent RNA transcripts by fluorescence in situ hybridization. Methods Mol Biol, 2010. 659: p. 33-50.
135. Wang, D.O., et al., A quick and simple FISH protocol with hybridization-sensitive fluorescent linear oligodeoxynucleotide probes. RNA, 2012. 18(1): p. 166-75.
由於X染色體在男女性別間具有不對稱遺傳的特性，進而造成與X染色體有關的基因組印記會伴隨著性別雙型性。根據本實驗室先前的核醣核酸定序資料，我們發現Ndufb11穩定的表現母方來源的等位基因。其原因為Ndufb11位於X染色體上，而我們先前又都使用公小鼠的核醣核酸來做定序。其實不只是Ndufb11，還有X染色體上的所有基因都會假性地表現母方來源的等位基因。因此，這次我們使用母小鼠的核醣核酸，且利用核酸質譜分析技術來驗證Ndufb11到底是否為一個與X染色體有關之母方表達印記基因。有趣的是，我們的數據指出Ndufb11在小鼠視覺皮質是一個特定種族 (CAST/EiJ) 之單方等位表達印記基因。
一般來說，我們都知道印記是動態的且會受到外在環境所調控，因此我們想瞭解印記基因是否會受到光線調控。我們透過將小鼠飼養在正常環境 (12小時光照、12小時黑暗) 以及無光線飼養 (24小時全黑暗) 的方式操弄小鼠模型的生活環境。然後，我們分別測量有光線及無光線飼養小鼠運動皮層的印記基因之核醣核酸表現量。理論上，我們推測他們之間應該會沒有顯著的差異。令人驚訝的是，我們發現在21個已知的印記基因中，Airn-160932和Copg2-48774的表現量在有光線及無光線飼養小鼠運動皮層間顯著地改變，但卻在小鼠視覺系統 (視覺皮層、視叉上核、視網膜) 維持穩定的表現量。我們認為在有光線及無光線飼養小鼠運動皮層間，此兩個印記基因表現量的改變可能是受到光線調控的次級效應所影響，而非初級效應。然而，這樣的假說還需要未來更多的證據支持才得以證實。
|dc.description.abstract||Genomic imprinting is a parent-of-origin effect which causes monoallelic gene expression. Dysregulation of imprinted genes is involved in various neurological and psychiatric disorders, but their roles in the brain are still unclear. Genomic imprinting is spatiotemporally dynamic, and varies between different species, experiences, tissues and cell types. NSCs have the capacity to self-renew and differentiate into new neurons of the central nervous system. NSCs are crucial to brain and are associated with several developmental disorders, neurodegenerative and psychiatric diseases. In fact, there had been already two studies reported the relationship between imprinted genes and NSCs. Consequently, we wanted to identify all the imprinted genes in the mouse NSCs. We used FACS technique to collect NSCs, extracted the RNA and sent for RNA sequencing (RNA-Seq). However, the immunofluorescence staining and RNA-Seq results were not as good as we hoped. We then tried to find another mouse model to achieve our goal.
X-linked imprinting can accompany with sexual dimorphism because of the asymmetrical inheritance of the X chromosome. Based on the previous RNA-Seq data in our lab, we found that Ndufb11 revealed stable maternal expression. That was because Ndufb11 is located on X chromosome, and we used male mouse sample to do the RNA-Seq. Actually, not only Ndufb11 but all the genes located on X chromosome would show falsely maternal expression. Therefore, this time we used female mice sample and MassArray system to validate whether Ndufb11 was an X-linked maternally expressed imprinted gene or not. Intriguingly, our data indicated that Ndufb11 was a strain-specific (CAST/EiJ-specific) monoallelic expressed gene in mouse visual cortex.
Generally speaking, we all known that imprinting is dynamic and can be regulated by the environment; hence we wanted to understand whether the imprinted genes can be regulated by the light. We manipulated the environment of mouse model by maintaining them in normal circadian cycle (normal-rearing) or complete darkness (dark-rearing). Then, we measured the imprinted genes mRNA expression level from normal- and dark-reared mouse motor cortex respectively. Theoretically, we supposed that it would be no significant change in normal- and dark-reared mouse motor cortex. Surprisingly, we found that among 21 known imprinted genes, Airn-160932 and Copg2-48774 expression changed significantly in mouse motor cortex under light manipulation, but their expression remain stable in mouse visual system (visual cortex, SCN and retina). We considered that the change of these two imprinted genes in normal- and dark-reared mouse motor cortex was possibly due to the secondary effect but not the primary effect of the light manipulation. However, this hypothesis still needs more evidence for further verification in the future.
On the basis of the previous Sanger sequencing and MassArray data in our lab, we discovered that Ago2 might be a partial maternally expressed gene not in the excitatory neurons, interneurons and astrocytes but in the other cell types in mouse visual cortex. We successfully established the RNA-FISH technique in our lab whereas we surprisingly found that the endogenous fluorescence disappeared after the boiling step of tissue sections preparation. Accordingly, we could not use the cell type-specific Cre transgenic mice to observe the Ago2 mRNA expression in specific cell types. Even so, we still succeeded to show both the monoallelic and biallelic expression pattern of Ago2 mRNA by using RNA-FISH technique. In summary, if we want to detect monoallelic or biallelic gene expression in specific cell types in the future, combine the RNA-FISH technique and immunofluorescent staining may be necessary.
|dc.description.provenance||Made available in DSpace on 2021-06-15T11:31:23Z (GMT). No. of bitstreams: 1|
ntu-105-R03454006-1.pdf: 7612503 bytes, checksum: 61f27a982cf4170ca52318876f920aec (MD5)
Previous issue date: 2016
PART 1 VIII
PART 2 XII
PART 3 XIV
PART 4 XVI
PART 1 — DETERMINATION OF THE GENOMIC IMPRINTING STATUS IN THE MOUSE EMBRYONIC AND ADULT NEURAL STEM CELL
Chapter 1 Introduction 2
1.1 Background of genomic imprinting 2
1.2 Dynamic feature of imprinted gene 4
1.3 Important role of neural stem cells in the brain 5
1.4 Imprinting in neural stem cells 7
Chapter 2 Material and Method 9
2.1 Mice 9
2.2 Fluorescence-activated cell sorting (FACS) 11
2.3 RNA extraction 13
2.4 Library construction 14
2.5 RNA sequencing and analysis 15
2.6 Quantitative real-time PCR (qRT-PCR) 15
2.7 Immunofluorescence staining 16
2.8 Statistical analysis 18
Chapter 3 Result 19
3.1 The recombination of Cre/loxP system mediates the red fluorescence of NSCs in Sox1-Cre::tdTomato mice 19
3.2 Embryonic and adult NSCs-specific RNA were collected respectively by fluorescence-activated cell sorting (FACS) 19
3.3 cDNA libraries of embryonic and adult NSCs met the RNA-Seq requirement 21
3.4 Sox1-Cre::tdTomato mice might not specifically labeled the NSCs in the brain at embryonic and adult stages 22
3.5 Different distribution patterns of tdTomato and GFP appeared in the E15.5 Sox1-Cre::tdTomato::GFP hybrid embryonic brain 23
3.6 RNA-Seq results of the hybrid offspring from Sox1-Cre::tdTomato reciprocal cross at embryonic and adult stages might not be reliable enough for further analysis 24
3.7 Another potential mouse model for this project — Fezf2-GFP mice 25
3.8 Adult Fezf2-GFP mice could be the mouse model of this project while Fezf2-GFP embryo could not 25
3.9 Adult NSCs in Fezf2-GFP mice hippocampi were collected by FACS 26
3.10 Cell identity testing of P- and N-group of cells collected after FACS 27
Chapter 4 Discussion 28
4.1 Limitation of the previous study 28
4.2 Summary of the result 29
Chapter 5 Figure and Table 32
Figure 1. Genome-wide profiling of imprinted genes in the embryonic and adult mouse NSCs 33
Figure 2. Genomic structure and genotyping of the offspring from the cross of Sox1-Cre x tdTomato 35
Figure 3. FACS diagrams of embryo whole brain and adult mouse hippocampus 36
Figure 4. qRT-PCR of tdTomato and Sox1 mRNA from embryonic and adult cells collected by FACS system 38
Figure 5. Quantity and quality of RNA extracted from P-group cells 39
Figure 6. Constructions of NSC-specific cDNA libraries at embryonic and adult stages 40
Figure 7. FACS diagrams and qRT-PCR analyses of excitatory neurons, interneurons and astrocytes in mouse whole cortex, as well as embryonic NSCs in embryo whole brain and adult NSCs in mouse hippocampus 42
Figure 8. False positive expression of Sox1 in adult mouse hippocampal dentate gyrus 44
Figure 9. Examination of Sox2 antibody 46
Figure 10. Expression of Sox2 and NeuN in embryonic brain and adult mouse hippocampal dentate gyrus 48
Figure 11. Expression of tdTomato and GFP in the Sox1-Cre::tdTomato::GFP embryonic brain 50
Figure 12. Heat map of immature and differentiated cell markers level in embryonic-tdTomato+ cells and adult-tdTomato+ cells, excitatory neurons, interneurons and astrocytes 51
Figure 13. Genomic structure and genotyping of the Fezf2-GFP mice 52
Figure 14. Expression of GFP in adult Fezf2-GFP mouse 54
Figure 15. Expression of GFP in Fezf2-GFP embryo 57
Figure 16. FACS diagrams of adult Fezf2-GFP mouse hippocampi 58
Figure 17. qRT-PCR of GFP, Nestin and Pax6 mRNA from P28 Fezf2-GFP mice hippocampi cells collected by FACS system 60
Chapter 6 Supplementary Data 61
Supplementary Figure 1. Expression of tdTomato and endogenous tdTomato in Sox1-Cre::tdTomato and Gfap-Cre::tdTomato mouse brain 62
Supplementary Figure 2. Parental expression levels of embryonic- and adult-tdTomato+ cells, as well as excitatory neurons, interneurons and astrocytes from reciprocal cross male mice 64
Supplementary Figure 3. References of Fezf2 expression in embryo and adult hippocampal dentate gyrus 65
PART 2 — VALIDATION OF THE X-LINKED IMPRINTED GENE CANDIDATE — NDUFB11
Chapter 1 Introduction 67
1.1 X chromosome 67
1.2 X chromosome inactivation (XCI) 67
1.2 X-linked imprinting 68
1.4 A candidate of X-linked imprinted gene — Ndufb11 70
Chapter 2 Material and Method 73
2.1 Analyzing previous RNA-Seq data 73
2.2 Mice 73
2.3 RNA extraction 73
2.4 cDNA conversion and PCR 74
2.5 MassArray 75
Chapter 3 Result 76
3.1 Ndufb11 showed falsely maternal expression in all the previous RNA-Seq data in our lab 76
3.2 Failures of Ndufb11-specific sequence isolation 76
3.3 Ndufb11 showed the strain-specific (CAST/EiJ-specific) monoallelic expression in adult mouse visual cortex by MassArray system 76
Chapter 4 Discussion 78
Chapter 5 Figure and Table 80
Table 1. Information of Ndufb11 from previous RNA-Seq data in our lab 81
Figure 1. Failures of Ndufb11-specific sequence isolation 82
Figure 2. Analyses of parental expression of genes by MassArray system 84
Chapter 6 Supplementary Data 85
Supplementary Figure 1. Inheritance of an X-linked imprinted trait conferring point coloration 86
Supplementary Table 1. Criteria for candidate imprinted genes selection 87
PART 3 — MEASURING THE EXPRESSION OF KNOWN IMPRINTED GENES IN THE MOUSE MOTOR CORTEX UNDER NORMAL- AND DARK-REARING CONDITIONS
Chapter 1 Introduction 89
Chapter 2 Material and Method 92
2.1 Mice 92
2.2 RNA extraction 92
2.3 Quantitative real-time PCR (qRT-PCR) 92
2.4 Statistical analysis 92
Chapter 3 Result 93
3.1 Among 21 known imprinted genes in mouse motor cortex, Airn-160932 and Copg2-48774 showed significant differences between normal- and dark-rearing conditions 93
3.2 Significance of Airn-160932 and Copg2-48774 expression revealed in mouse motor cortex between normal- and dark-rearing conditions, but not revealed in mouse visual cortex, SCN and retina 93
Chapter 4 Discussion 94
Chapter 5 Figure and Table 96
Table 1. Primers list of qRT-PCR 96
Table 2. Expression of 21 known imprinted genes in normal- and dark-reared mouse motor cortex 98
Figure 1. qRT-PCR of Airn-160932 and Copg2-48774 mRNA from mouse motor cortex, visual cortex, SCN and retina under normal- and dark-rearing conditions 100
Chapter 6 Supplementary Data 101
Supplementary Figure 1. Changes of gene expression and circadian rhythm under dark-reared manipulation 102
Supplementary Table 1. Expression of Airn-160932 and Copg2-48774 in normal- and dark-reared mouse visual cortex, SCN and retina 104
PART 4 — ESTABLISHING A RELIABLE PLATFORM FOR DETECTING MONOALLELIC GENE EXPRESSION IN SITU
Chapter 1 Introduction 106
Chapter 2 Material and Method 108
2.1 Mice 108
2.2 MassArray 108
2.3 RNA-Fluorescence in situ hybridization (RNA-FISH) 108
Chapter 3 Result 110
3.1 Ago2 in mouse visual cortex revealed preferential maternal expression by Sanger sequencing and MassArray system but it showed biallelic expression among mouse whole cortex excitatory neurons, interneurons and astrocytes from Sanger sequencing results 110
3.2 Endogenous red fluorescence disappeared after the boiling step of tissue sections preparation 110
3.3 RNA-FISH technique procedure was well-built in our lab 111
3.4 Observation of Ago2 monoallelic and biallelic expression by RNA-FISH technique 111
Chapter 4 Discussion 112
Chapter 5 Figure and Table 116
Figure 1. Information of Ago2 from previous Sanger sequencing and MassArray data in our lab 117
Figure 2. Comparison of sections before and after boiling step 118
Figure 3. Validation of RNA-FISH technique 120
Figure 4. Distribution pattern of Ago2 by RNA-FISH technique 121
Chapter 6 Supplementary Data 122
Supplementary Table 1. Information of Ago2 from previous RNA-Seq data in our lab 122
|dc.title||Investigation of Genomic Imprinting in the Mouse Brain — Methodological Point of View||en|
|dc.contributor.oralexamcommittee||林劭品(Shau-Ping Lin),莊樹諄(Trees-Juen Chuang),陳俊安(Jun-An Chen)|
|dc.subject.keyword||genomic imprinting,X-linked imprinting,monoallelic expression,strain-specific monoallelic expression,neural stem cell (NSC),motor cortex,visual cortex,light manipulation,fluorescence-activated cell sorting (FACS),immunofluorescence staining,fluorescence in situ hybridization (FISH),RNA sequencing,MassArray,Ndufb11,Ago2,||en|
|Appears in Collections:||腦與心智科學研究所|
Files in This Item:
|7.43 MB||Adobe PDF|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.