博碩士論文 105821021 詳細資訊

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姓名 王又婷(Yu-Ting Wang)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 探討斑馬魚ttbk2a和ttbk2b的功能
(Investigation of ttbk2a and ttbk2b function in the zebrafish)
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摘要(中) 初級纖毛在脊椎動物的神經系統發育中扮演非常重要的角色,然而,目前對於初級纖毛是如何去影響神經系統的機制仍然不是很清楚。Tau tubulin kinase 2 (TTBK2) 是一個表現在腦中用來調節初級纖毛形成的重要因子,TTBK2的突變將會造成脊髓小腦萎縮症,患者的小腦會有萎縮的現象。由此可知,TTBK2對於腦的發育形成非常重要,但其中的機制依然不是很了解。所以,在本篇研究中,我選擇利用斑馬魚研究ttbk2a以及ttbk2b的表現與功能。我利用RT-PCR及原位雜交法觀察ttbk2a及ttbk2b的mRNA表現,我發現在斑馬魚出生後第三天,ttbk2a及ttbk2b都開始有表現,但其中只有ttbk2b在出生的時候就開始表現到出生5.25小時候表現下降。從原位雜交法中,我發現ttbk2a及ttbk2b的mRNA表現在許多腦區,例如: ventral telencephalic area, medial zone of dorsal telencephalic area, periventricular grey zone of optic tectum, lateral division of valvula cerebelli, and corpus cerebelli。另外,為了探討ttbk2基因的功能,我利用CRISPRC-Cas9系統去做基因編輯,進而去模仿人類的疾病模式以及破壞掉ttbk2中最重要的區域。目前,已經建立出一系列的突變魚。初步我看到了一些突變魚的游泳能力下降。利用這些魚我們可以進一步探討ttbk2以及初級纖毛在腦中扮演的角色。
摘要(英) The primary cilium plays a critical role in the development of vertebrate nervous system. However, the function of primary cilia in brain remains unclear. Tau tubulin kinase 2 (TTBK2) is a regulator required for primary cilium formation, and its transcript can be detected in the brain. In human, mutations in TTBK2 serine rich domain cause spinocerebellar ataxia type 11 (SCA11) and the cerebellum will undergo degeneration. TTBK2 is essential for brain development, yet the mechanism is still elusive. Therefore, I focus on ttbk2a and ttbk2b in zebrafish. Zebrafish is a powerful model for the study of human disease.
In this study, I characterized ttbk2a and ttbk2b RNA expression pattern during embryogenesis and in the adult tissues using RT-PCR and in situ hybridization. The ttbk2a and ttbk2b transripts started to be expressed after 3 dpf, and ttbk2b was also expressed transiently from the 1-cell stage to 50% epiboly. Both ttbk2a and ttbk2b transcripts were detected in several adult fish brain regions, such as ventral telencephalic area (Vd), medial zone of dorsal telencephalic area (Dm), periventricular grey zone of optic tectum (PGZ), lateral division of valvula cerebelli (Val), and corpus cerebelli (Cce).
To investigate ttbk2 function, I generated ttbk2 mutants by CRISPR-Cas9 system to create mutations mimicking human patients and disrupting the most important domains of ttbk2. I already obtained 5 lines of F1 fish. One G0 fish had reduced ability to swim in the swim tunnel assay, indicating that ttbk2 mutation may affect zebrafish swimming behavior. These mutant fish will be a useful tool to investigate the function and mechanism of ttbk2 and primary cilia.
關鍵字(中) ★ ttbk2a
★ ttbk2b
★ 斑馬魚
★ 腦
★ 纖毛
關鍵字(英) ★ ttbk2a
★ ttbk2b
★ zebrafish
★ brain
★ cilia
論文目次 摘要 I
Abstract II
Table of content III
List of Tables VI
List of Figures VII
Abbreviation IX
Chapter 1 Introduction 1
1.1 cilia 1
˙structure of cilia 1
˙function of cilia 2
˙ciliopathies 3
˙ciliogenesis 4
˙IFT machinery 4
˙regulators involved in ciliogenesis 5
˙signaling pathways that regulate ciliogenesis 6
1.2 brain development 7
˙cilia in the brain development 7
˙zebrafish brain development 7
1.3 Tau Tubulin Kinase (TTBK) 8
˙Tau Tubulin Kinase 1 (TTBK1) 9
˙Tau Tubulin Kinase 2 (TTBK2) 9
˙TTBK2 and ciliogenesis 10
˙Spinocerebellar Ataxia Type 11 (SCA11) 11
1.4 Motivation 12
Chapter 2 Materials and Methods 13
2.1 Fish rearing 13
2.2 Phylogenetic analysis 13
2.3 Sequence homology analysis 14
2.4 RNA extraction 14
2.5 Reverse-transcriptase RCR (RT-PCR) 14
2.6 Plasmids 15
2.7 RNA probe synthesis 16
2.8 In situ hybridization 16
2.9 cell culture 17
2.10 Immunofluorescence 18
2.11 Generation of knockout fish by CRISPR-Cas9 18
2.12 Genotyping and measurement of KO efficiency 19
2.13 Capillary Electrophoresis 20
2.14 Photography and Microscopy 20
2.15 Behavior test 20
2.16 Statistical analysis 21
Chapter 3 Results 22
3.1 Phylogenetic analysis of zebrafish ttbk genes. 22
3.2 Spatiotemporal expression of zebrafish ttbk2 paralog genes. 22
3.3 ttbk2a and ttbk2b mRNA expression in adult zebrafish brain. 23
3.4 Zebrafish ttbk2 protein expression in the base of cilia. 24
3.5 Generation of ttbk2a and ttbk2b mutant fish by CRISPR-Cas9 system. 24
3.6 Behavior test of adult ttbk2a and ttbk2b G0 founder fish. 27
Chapter 4 Discussions 29
4.1 Role of ttbk2b in zebrafish early stage. 29
4.2 Comparison of ttbk2a and ttbk2b. 29
4.3 The expression of ttbk2 protein in vertebrates. 30
4.4 The analysis of ttbk2a and ttbk2b mutant fish. 31
Chapter 5 Future experiments 33
5.1 Characterized the protein expression of TTBK2 in the zebrafish 33
5.2 Generation and analysis of ttbk2a mutant fish and ttbk2b mutant fish 33
5.3 To explore the mechanism of ttbk2 34
References 35
Figure legends 52
參考文獻 Almilaji, A., Munoz, C., Hosseinzadeh, Z., and Lang, F. (2013). Upregulation of Na+,Cl(-)-coupled betaine/gamma-amino-butyric acid transporter BGT1 by Tau tubulin kinase 2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 32, 334-343.

Amador-Arjona, A., Elliott, J., Miller, A., Ginbey, A., Pazour, G.J., Enikolopov, G., Roberts, A.J., and Terskikh, A.V. (2011). Primary cilia regulate proliferation of amplifying progenitors in adult hippocampus: implications for learning and memory. The Journal of neuroscience : the official journal of the Society for Neuroscience 31, 9933-9944.

Archer, F.L., and Wheatley, D.N. (1971). Cilia in cell-cultured fibroblasts. II. Incidence in mitotic and post-mitotic BHK 21-C13 fibroblasts. Journal of anatomy 109, 277-292.

Asai, H., Ikezu, S., Woodbury, M.E., Yonemoto, G.M., Cui, L., and Ikezu, T. (2014). Accelerated neurodegeneration and neuroinflammation in transgenic mice expressing P301L tau mutant and tau-tubulin kinase 1. The American journal of pathology 184, 808-818.

Atwood, S.X., Li, M., Lee, A., Tang, J.Y., and Oro, A.E. (2013). GLI activation by atypical protein kinase C iota/lambda regulates the growth of basal cell carcinomas. Nature 494, 484-488.

Badano, J.L., Mitsuma, N., Beales, P.L., and Katsanis, N. (2006). The ciliopathies: an emerging class of human genetic disorders. Annual review of genomics and human genetics 7, 125-148.

Bae, Y.K., Kani, S., Shimizu, T., Tanabe, K., Nojima, H., Kimura, Y., Higashijima, S., and Hibi, M. (2009). Anatomy of zebrafish cerebellum and screen for mutations affecting its development. Developmental biology 330, 406-426.

Bender, C., and Ullrich, A. (2012). PRKX, TTBK2 and RSK4 expression causes Sunitinib resistance in kidney carcinoma- and melanoma-cell lines. International journal of cancer 131, E45-55.

Blacque, O.E., and Leroux, M.R. (2006). Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport. Cellular and molecular life sciences : CMLS 63, 2145-2161.

Blacque, O.E., Li, C., Inglis, P.N., Esmail, M.A., Ou, G., Mah, A.K., Baillie, D.L., Scholey, J.M., and Leroux, M.R. (2006). The WD repeat-containing protein IFTA-1 is required for retrograde intraflagellar transport. Molecular biology of the cell 17, 5053-5062.

Blaser, R., and Gerlai, R. (2006). Behavioral phenotyping in zebrafish: Comparison of three behavioral quantification methods. Behavior Research Methods 38, 456-469.
Boltshauser, E., and Isler, W. (1977). Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis. Neuropadiatrie 8, 57-66.

Borovina, A., Superina, S., Voskas, D., and Ciruna, B. (2010). Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia. Nat Cell Biol 12, 407-412.

Bouskila, M., Esoof, N., Gay, L., Fang, E.H., Deak, M., Begley, M.J., Cantley, L.C., Prescott, A., Storey, K.G., and Alessi, D.R. (2011). TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development. The Biochemical journal 437, 157-167.

Brett, J.R. (1964). The Respiratory Metabolism and Swimming Performance of Young Sockeye Salmon. Journal of the Fisheries Research Board of Canada 21, 1183-1226.

Budny, B., Chen, W., Omran, H., Fliegauf, M., Tzschach, A., Wisniewska, M., Jensen, L.R., Raynaud, M., Shoichet, S.A., Badura, M., et al. (2006). A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Human genetics 120, 171-178.

Christensen, S.T., Pedersen, L.B., Schneider, L., and Satir, P. (2007). Sensory cilia and integration of signal transduction in human health and disease. Traffic (Copenhagen, Denmark) 8, 97-109.

Corbit, K.C., Aanstad, P., Singla, V., Norman, A.R., Stainier, D.Y., and Reiter, J.F. (2005). Vertebrate Smoothened functions at the primary cilium. Nature 437, 1018-1021.

Corbit, K.C., Shyer, A.E., Dowdle, W.E., Gaulden, J., Singla, V., Chen, M.H., Chuang, P.T., and Reiter, J.F. (2008). Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol 10, 70-76.

Cuny, G.D. (2009). Kinase inhibitors as potential therapeutics for acute and chronic neurodegenerative conditions. Current pharmaceutical design 15, 3919-3939.

Dahmane, N., and Ruiz i Altaba, A. (1999). Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 126, 3089-3100.

Doherty, D. (2009). Joubert syndrome: insights into brain development, cilium biology, and complex disease. Seminars in pediatric neurology 16, 143-154.

Doi, H., Yoshida, K., Yasuda, T., Fukuda, M., Fukuda, Y., Morita, H., Ikeda, S., Kato, R., Tsurusaki, Y., Miyake, N., et al. (2011). Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomal-recessive spinocerebellar ataxia with psychomotor retardation. American journal of human genetics 89, 320-327.

Dryja, T.P., Adams, S.M., Grimsby, J.L., McGee, T.L., Hong, D.H., Li, T., Andreasson, S., and Berson, E.L. (2001). Null RPGRIP1 alleles in patients with Leber congenital amaurosis. American journal of human genetics 68, 1295-1298.

Farris, J.S. (1970). Methods for Computing Wagner Trees. Systematic Zoology 19, 83-92.

Gagnon, J.A., Valen, E., Thyme, S.B., Huang, P., Akhmetova, L., Pauli, A., Montague, T.G., Zimmerman, S., Richter, C., and Schier, A.F. (2014). Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PloS one 9, e98186.

Garcia-Gonzalo, F.R., Corbit, K.C., Sirerol-Piquer, M.S., Ramaswami, G., Otto, E.A., Noriega, T.R., Seol, A.D., Robinson, J.F., Bennett, C.L., Josifova, D.J., et al. (2011). A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet 43, 776-784.

Gilula, N.B., and Satir, P. (1972). The ciliary necklace. A ciliary membrane specialization. The Journal of cell biology 53, 494-509.

Goetz, S.C., Liem, K.F., Jr., and Anderson, K.V. (2012). The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis. Cell 151, 847-858.

Graser, S., Stierhof, Y.D., Lavoie, S.B., Gassner, O.S., Lamla, S., Le Clech, M., and Nigg, E.A. (2007). Cep164, a novel centriole appendage protein required for primary cilium formation. The Journal of cell biology 179, 321-330.

Gupta, T., and Mullins, M.C. (2010). Dissection of Organs from the Adult Zebrafish. Journal of Visualized Experiments : JoVE, 1717.

Han, Y.-G., and Alvarez-Buylla, A. (2010). Role of primary cilia in brain development and cancer. Current Opinion in Neurobiology 20, 58-67.

Haycraft, C.J., Banizs, B., Aydin-Son, Y., Zhang, Q., Michaud, E.J., and Yoder, B.K. (2005). Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS genetics 1, e53.

Hibi, M., and Shimizu, T. (2012). Development of the cerebellum and cerebellar neural circuits. Developmental neurobiology 72, 282-301.

Hildebrandt, F., Benzing, T., and Katsanis, N. (2011). Ciliopathies. The New England journal of medicine 364, 1533-1543.

Hirokawa, N., Tanaka, Y., Okada, Y., and Takeda, S. (2006). Nodal flow and the generation of left-right asymmetry. Cell 125, 33-45.

Houlden, H., Johnson, J., Gardner-Thorpe, C., Lashley, T., Hernandez, D., Worth, P., Singleton, A.B., Hilton, D.A., Holton, J., Revesz, T., et al. (2007). Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nature Genetics 39, 1434.

Huangfu, D., Liu, A., Rakeman, A.S., Murcia, N.S., Niswander, L., and Anderson, K.V. (2003). Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83-87.
Hwang, W.Y., Fu, Y., Reyon, D., Maeder, M.L., Tsai, S.Q., Sander, J.D., Peterson, R.T., Yeh, J.R., and Joung, J.K. (2013). Efficient genome editing in zebrafish using a CRISPR-Cas system. Nature biotechnology 31, 227-229.

Ibanez-Tallon, I., Pagenstecher, A., Fliegauf, M., Olbrich, H., Kispert, A., Ketelsen, U.P., North, A., Heintz, N., and Omran, H. (2004). Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Human molecular genetics 13, 2133-2141.

Ikezu, S., and Ikezu, T. (2014). Tau-tubulin kinase. Frontiers in Molecular Neuroscience 7.

Insinna, C., and Besharse, J.C. (2008). Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors. Developmental dynamics : an official publication of the American Association of Anatomists 237, 1982-1992.

Iomini, C., Babaev-Khaimov, V., Sassaroli, M., and Piperno, G. (2001). Protein particles in Chlamydomonas flagella undergo a transport cycle consisting of four phases. The Journal of cell biology 153, 13-24.

Ishikawa, H., and Marshall, W.F. (2011). Ciliogenesis: building the cell′s antenna. Nature reviews Molecular cell biology 12, 222-234.

Jao, L.E., Wente, S.R., and Chen, W. (2013). Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proceedings of the National Academy of Sciences of the United States of America 110, 13904-13909.

Jin, H., White, S.R., Shida, T., Schulz, S., Aguiar, M., Gygi, S.P., Bazan, J.F., and Nachury, M.V. (2010). The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell 141, 1208-1219.

Joo, K., Kim, C.G., Lee, M.S., Moon, H.Y., Lee, S.H., Kim, M.J., Kweon, H.S., Park, W.Y., Kim, C.H., Gleeson, J.G., et al. (2013). CCDC41 is required for ciliary vesicle docking to the mother centriole. Proceedings of the National Academy of Sciences of the United States of America 110, 5987-5992.

Kaslin, J., and Brand, M. (2016). The Zebrafish Cerebellum. In Essentials of Cerebellum and Cerebellar Disorders (Springer), pp. 411-421.
Kulaga, H.M., Leitch, C.C., Eichers, E.R., Badano, J.L., Lesemann, A., Hoskins, B.E., Lupski, J.R., Beales, P.L., Reed, R.R., and Katsanis, N. (2004). Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat Genet 36, 994-998.

Kumar, S., Stecher, G., and Tamura, K. (2016). MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. Molecular biology and evolution 33, 1870-1874.

Liachko, N.F., McMillan, P.J., Strovas, T.J., Loomis, E., Greenup, L., Murrell, J.R., Ghetti, B., Raskind, M.A., Montine, T.J., Bird, T.D., et al. (2014). The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43. PLoS genetics 10, e1004803.

Liao, J.-C., Yang, T.T., Weng, R.R., Kuo, C.-T., and Chang, C.-W. (2015). TTBK2: A Tau Protein Kinase beyond Tau Phosphorylation. BioMed research international 2015, 575170.
Lowery, L.A., and Sive, H. (2005). Initial formation of zebrafish brain ventricles occurs independently of circulation and requires the nagie oko and snakehead/atp1a1a.1 gene products. Development 132, 2057-2067.

Lund, H., Cowburn, R.F., Gustafsson, E., Stromberg, K., Svensson, A., Dahllund, L., Malinowsky, D., and Sunnemark, D. (2013). Tau-tubulin kinase 1 expression, phosphorylation and co-localization with phospho-Ser422 tau in the Alzheimer′s disease brain. Brain pathology (Zurich, Switzerland) 23, 378-389.

Lyons, R.A., Saridogan, E., and Djahanbakhch, O. (2006). The reproductive significance of human Fallopian tube cilia. Human reproduction update 12, 363-372.

Marion, V., Stoetzel, C., Schlicht, D., Messaddeq, N., Koch, M., Flori, E., Danse, J.M., Mandel, J.L., and Dollfus, H. (2009). Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proceedings of the National Academy of Sciences of the United States of America 106, 1820-1825.

Matilla-Duenas, A. (2012). The ever expanding spinocerebellar ataxias. Editorial. Cerebellum (London, England) 11, 821-827.

McIntyre, M., and Stein, D.G. (1973). Differential effects of one- vs two-stage amygdaloid lesions on activity, exploratory, and avoidance behavior in the albino rat. Behavioral biology 9, 451-465.

Meek, J. (1992). Comparative aspects of cerebellar organization. From mormyrids to mammals. European journal of morphology 30, 37-51.

Morgan, D., Eley, L., Sayer, J., Strachan, T., Yates, L.M., Craighead, A.S., and Goodship, J.A. (2002). Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle. Human molecular genetics 11, 3345-3350.

Mukhopadhyay, S., and Rohatgi, R. (2014). G-protein-coupled receptors, Hedgehog signaling and primary cilia. Seminars in cell & developmental biology 33, 63-72.

Nachury, M.V., Loktev, A.V., Zhang, Q., Westlake, C.J., Peranen, J., Merdes, A., Slusarski, D.C., Scheller, R.H., Bazan, J.F., Sheffield, V.C., et al. (2007). A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129, 1201-1213.

Narita, K., Kawate, T., Kakinuma, N., and Takeda, S. (2010). Multiple primary cilia modulate the fluid transcytosis in choroid plexus epithelium. Traffic (Copenhagen, Denmark) 11, 287-301.

Nielsen, S.K., Mollgard, K., Clement, C.A., Veland, I.R., Awan, A., Yoder, B.K., Novak, I., and Christensen, S.T. (2008). Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines. Developmental dynamics : an official publication of the American Association of Anatomists 237, 2039-2052.

Pazour, G.J., Dickert, B.L., Vucica, Y., Seeley, E.S., Rosenbaum, J.L., Witman, G.B., and Cole, D.G. (2000). Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. The Journal of cell biology 151, 709-718.

Pedersen, L.B., and Rosenbaum, J.L. (2008). Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling. Current topics in developmental biology 85, 23-61.
Pelegri, F. (2003). Maternal factors in zebrafish development. Developmental dynamics : an official publication of the American Association of Anatomists 228, 535-554.

Portavella, M., Torres, B., and Salas, C. (2004). Avoidance Response in Goldfish: Emotional and Temporal Involvement of Medial and Lateral Telencephalic Pallium. The Journal of Neuroscience 24, 2335-2342.

Qi, H., Yao, C., Cai, W., Girton, J., Johansen, K.M., and Johansen, J. (2009). Asator, a tau-tubulin kinase homolog in Drosophila localizes to the mitotic spindle. Developmental dynamics : an official publication of the American Association of Anatomists 238, 3248-3256.

Reiter, J.F., and Leroux, M.R. (2017). Genes and molecular pathways underpinning ciliopathies. Nature reviews Molecular cell biology 18, 533-547.

Rohatgi, R., Milenkovic, L., and Scott, M.P. (2007). Patched1 regulates hedgehog signaling at the primary cilium. Science (New York, NY) 317, 372-376.

Ross, A.J., May-Simera, H., Eichers, E.R., Kai, M., Hill, J., Jagger, D.J., Leitch, C.C., Chapple, J.P., Munro, P.M., Fisher, S., et al. (2005). Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 37, 1135-1140.

Rossi, A., Kontarakis, Z., Gerri, C., Nolte, H., Holper, S., Kruger, M., and Stainier, D.Y.R. (2015). Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524, 230.

Saggese, T., Young, A.A., Huang, C., Braeckmans, K., and McGlashan, S.R. (2012). Development of a method for the measurement of primary cilia length in 3D. Cilia 1, 11.

Satir, P., and Christensen, S.T. (2007). Overview of structure and function of mammalian cilia. Annual review of physiology 69, 377-400.

Satir, P., and Sleigh, M.A. (1990). The physiology of cilia and mucociliary interactions. Annual review of physiology 52, 137-155.

Sato, S., Cerny, R.L., Buescher, J.L., and Ikezu, T. (2006). Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation. Journal of neurochemistry 98, 1573-1584.

Sato, S., Xu, J., Okuyama, S., Martinez, L.B., Walsh, S.M., Jacobsen, M.T., Swan, R.J., Schlautman, J.D., Ciborowski, P., and Ikezu, T. (2008). Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1. The Journal of neuroscience : the official journal of the Society for Neuroscience 28, 14511-14521.

Sawamoto, K., Wichterle, H., Gonzalez-Perez, O., Cholfin, J.A., Yamada, M., Spassky, N., Murcia, N.S., Garcia-Verdugo, J.M., Marin, O., Rubenstein, J.L., et al. (2006). New neurons follow the flow of cerebrospinal fluid in the adult brain. Science (New York, NY) 311, 629-632.

Schier, A.F., Neuhauss, S.C., Harvey, M., Malicki, J., Solnica-Krezel, L., Stainier, D.Y., Zwartkruis, F., Abdelilah, S., Stemple, D.L., Rangini, Z., et al. (1996). Mutations affecting the development of the embryonic zebrafish brain. Development 123, 165-178.

Schmidt, T.I., Kleylein-Sohn, J., Westendorf, J., Le Clech, M., Lavoie, S.B., Stierhof, Y.D., and Nigg, E.A. (2009). Control of centriole length by CPAP and CP110. Current biology : CB 19, 1005-1011.

Schneider, L., Clement, C.A., Teilmann, S.C., Pazour, G.J., Hoffmann, E.K., Satir, P., and Christensen, S.T. (2005). PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Current biology : CB 15, 1861-1866.

Seifert, J.R., and Mlodzik, M. (2007). Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nature reviews Genetics 8, 126-138.

Shah, A.N., Davey, C.F., Whitebirch, A.C., Miller, A.C., and Moens, C.B. (2015). Rapid reverse genetic screening using CRISPR in zebrafish. Nature methods 12, 535-540.

Sillibourne, J.E., Specht, C.G., Izeddin, I., Hurbain, I., Tran, P., Triller, A., Darzacq, X., Dahan, M., and Bornens, M. (2011). Assessing the localization of centrosomal proteins by PALM/STORM nanoscopy. Cytoskeleton (Hoboken, NJ) 68, 619-627.

Singla, V., Romaguera-Ros, M., Garcia-Verdugo, J.M., and Reiter, J.F. (2010). Ofd1, a human disease gene, regulates the length and distal structure of centrioles. Developmental cell 18, 410-424.

Smith, J.L., and Schoenwolf, G.C. (1989). Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation. The Journal of experimental zoology 250, 49-62.

Sorokin, S. (1962). Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells. The Journal of cell biology 15, 363-377.

Spektor, A., Tsang, W.Y., Khoo, D., and Dynlacht, B.D. (2007). Cep97 and CP110 suppress a cilia assembly program. Cell 130, 678-690.

Suster, M.L., Kikuta, H., Urasaki, A., Asakawa, K., and Kawakami, K. (2009). Transgenesis in zebrafish with the tol2 transposon system. Methods in molecular biology (Clifton, NJ) 561, 41-63.

Takahashi, K. (1984). Cilia and flagella. Cell structure and function 9 Suppl, s87-90.
Takahashi, M., Tomizawa, K., Sato, K., Ohtake, A., and Omori, A. (1995). A novel tau-tubulin kinase from bovine brain. FEBS letters 372, 59-64.

Tallila, J., Jakkula, E., Peltonen, L., Salonen, R., and Kestila, M. (2008). Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle. American journal of human genetics 82, 1361-1367.

Tanos, B.E., Yang, H.J., Soni, R., Wang, W.J., Macaluso, F.P., Asara, J.M., and Tsou, M.F. (2013). Centriole distal appendages promote membrane docking, leading to cilia initiation. Genes & development 27, 163-168.

Taschner, M., and Lorentzen, E. (2016). The Intraflagellar Transport Machinery. Cold Spring Harbor perspectives in biology 8.

Tomizawa, K., Omori, A., Ohtake, A., Sato, K., and Takahashi, M. (2001). Tau-tubulin kinase phosphorylates tau at Ser-208 and Ser-210, sites found in paired helical filament-tau. FEBS letters 492, 221-227.

Torban, E., Kor, C., and Gros, P. (2004a). Van Gogh-like2 (Strabismus) and its role in planar cell polarity and convergent extension in vertebrates. Trends in genetics : TIG 20, 570-577.

Torban, E., Wang, H.J., Groulx, N., and Gros, P. (2004b). Independent mutations in mouse Vangl2 that cause neural tube defects in looptail mice impair interaction with members of the Dishevelled family. The Journal of biological chemistry 279, 52703-52713.

Tsao, C.C., and Gorovsky, M.A. (2008). Different effects of Tetrahymena IFT172 domains on anterograde and retrograde intraflagellar transport. Molecular biology of the cell 19, 1450-1461.

Varshney, G.K., Pei, W., LaFave, M.C., Idol, J., Xu, L., Gallardo, V., Carrington, B., Bishop, K., Jones, M., Li, M., et al. (2015). High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Genome research 25, 1030-1042.

Watanabe, D., Saijoh, Y., Nonaka, S., Sasaki, G., Ikawa, Y., Yokoyama, T., and Hamada, H. (2003). The left-right determinant Inversin is a component of node monocilia and other 9+0 cilia. Development 130, 1725-1734.

Westerfield, M. (2000). The Zebrafish Book. A Guide for The Laboratory Use of Zebrafish (Danio rerio), Vol 385.

Williams, C.L., Li, C., Kida, K., Inglis, P.N., Mohan, S., Semenec, L., Bialas, N.J., Stupay, R.M., Chen, N., Blacque, O.E., et al. (2011). MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis. The Journal of cell biology 192, 1023-1041.

Winocur, G. (1997). Hippocampal lesions alter conditioning to conditional and contextual stimuli. Behavioural brain research 88, 219-229.

Xu, J., Tsutsumi, K., Tokuraku, K., Estes, K.A., Hisanaga, S., and Ikezu, T. (2011). Actin interaction and regulation of cyclin-dependent kinase 5/p35 complex activity. Journal of neurochemistry 116, 192-204.

Ye, X., Zeng, H., Ning, G., Reiter, J.F., and Liu, A. (2014). C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals. Proceedings of the National Academy of Sciences of the United States of America 111, 2164-2169.

Yoder, B.K. (2007). Role of primary cilia in the pathogenesis of polycystic kidney disease. Journal of the American Society of Nephrology : JASN 18, 1381-1388.
Youn, Y.H., and Han, Y.G. (2018). Primary Cilia in Brain Development and Diseases. The American journal of pathology 188, 11-22.

Zhang, X.M., Ramalho-Santos, M., and McMahon, A.P. (2001). Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell 106, 781-792.
指導教授 鍾邦柱(Bon-Chu Chung) 審核日期 2018-7-31
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