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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃佩欣(Pei-Hsin Huang) | |
| dc.contributor.author | I-Chun Hsieh | en |
| dc.contributor.author | 謝宜君 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:57:28Z | - |
| dc.date.available | 2016-10-07 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-09 | |
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The microRNA bantam Functions in Epithelial Cells to Regulate Scaling Growth of Dendrite Arbors in Drosophila Sensory Neurons. Neuron, 63(6), 788-802. doi: 10.1016/j.neuron.2009.08.006 Qui, M. S., & Green, S. H. (1992). PC12 cell neuronal differentiation is associated with prolonged p21ras activity and consequent prolonged ERK activity. Neuron, 9(4), 705-717. Roffe, M., Beraldo, F. H., Bester, R., Nunziante, M., Bach, C., Mancini, G., . . . Hajj, G. N. M. (2010). Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR. Proceedings of the National Academy of Sciences, 107(29), 13147-13152. doi: 10.1073/pnas.1000784107 Rolls, M. M., & Doe, C. Q. (2004). Baz, Par-6 and aPKC are not required for axon or dendrite specification in Drosophila. Nature Neuroscience, 7(12), 1293-1295. doi: 10.1038/nn1346 Rolls, M. M., Satoh, D., Clyne, P. J., Henner, A. L., Uemura, T., & Doe, C. Q. (2007). Polarity and intracellular compartmentalization of Drosophila neurons. Neural Development, 2(1), 7. doi: 10.1186/1749-8104-2-7 Sánchez-Soriano, N., Tear, G., Whitington, P., & Prokop, A. (2007). Drosophila as a genetic and cellular model for studies on axonal growth. Neural Development, 2(1), 9. doi: 10.1186/1749-8104-2-9 St Johnston, D. (2002). The Art and Design of Genetic Screens: Drosophila Melanogaster. Nature Reviews Genetics, 3(3), 176-188. doi: 10.1038/nrg751 Takei, N. (2001). Brain-derived Neurotrophic Factor Enhances Neuronal Translation by Activating Multiple Initiation Processes. COMPARISON WITH THE EFFECTS OF INSULIN. Journal of Biological Chemistry, 276(46), 42818-42825. doi: 10.1074/jbc.M103237200 Tayler, T. D. (2004). Compartmentalization of visual centers in the Drosophila brain requires Slit and Robo proteins. Development, 131(23), 5935-5945. doi: 10.1242/dev.01465 Tettamanti, M., Armstrong, J. D., Endo, K., Yang, M. Y., Furukubo-Tokunaga, K., Kaiser, K., & Reichert, H. (1997). Early development of the Drosophila mushroom bodies, brain centres for associative learning and memory. Development Genes and Evolution, 207(4), 242-252. doi: 10.1007/s004270050112 Thomas, G. M., & Huganir, R. L. (2004). Mapk cascade signalling and synaptic plasticity. [Review]. Nature Reviews Neuroscience, 5(3), 173-183. doi: 10.1038/nrn1346 Weeber, E. J., & Sweatt, J. D. (2002). Molecular neurobiology of human cognition. [Review]. Neuron, 33(6), 845-848. Wu, S. H., Arévalo, J. C., Sarti, F., Tessarollo, L., Gan, W.-B., & Chao, M. V. (2009). Ankyrin Repeat-rich Membrane Spanning/Kidins220 protein regulates dendritic branching and spine stabilityin vivo. Developmental Neurobiology, 69(9), 547-557. doi: 10.1002/dneu.20723 Xiang, Y., Yuan, Q., Vogt, N., Looger, L. L., Jan, L. Y., & Jan, Y. N. (2010). Light-avoidance-mediating photoreceptors tile the Drosophila larval body wall. Nature, 468(7326), 921-926. doi: 10.1038/nature09576 Zhong, L., Hwang, R. Y., & Tracey, W. D. (2010). Pickpocket Is a DEG/ENaC Protein Required for Mechanical Nociception in Drosophila Larvae. Current Biology, 20(5), 429-434. doi: 10.1016/j.cub.2009.12.057 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/38028 | - |
| dc.description.abstract | ARMS (Ankyrin repeat-rich membrane spanning)，也稱 Kindins220 (kinase D-interacting substrate of 220 kDa)，是在演化上從線蟲到人類都有的高度保留基因。ARMS可以在許多組織中被偵測到，尤其最大量表現在發育中或成體的神經組織中，暗示其在神經系統中的重要性。之前的研究指出ARMS是酪胺酸激酶受體的下游分子，將訊號傳遞經由有絲分裂原激活蛋白激酶途徑(mitogen-activated protein kinase, MAPK)來引發有絲分裂原激活蛋白激酶持續的磷酸化，進而調控神經元的極性與神經纖維的生長。
此篇我們利用果蠅遺傳學來研究ARMS在神經系統中所扮演的角色。先前實驗室已發現在幼蟲時期,將眼碟經由核醣核酸干擾(RNA interference)使其ARMS減少，會造成成蟲複眼缺陷。此結果驅使我們更進一步去細究是否那些缺陷是發生在更早的發育時期。在檢視三齡幼蟲時期之果蠅視葉(optic lobe)的光受器1到8 (R1-R8)之後，並未發現任何缺陷。我們也檢查在三齡幼蟲晚期的其他神經器官，包括蕈狀體 (嗅覺學習與記憶中心)、腹部神經索(用來處理與傳送感覺神經傳來的訊號以及將訊號傳遞給運動神經)和周邊神經，觀察ARMS減少時是否會對其造成影響。結果顯示蕈狀體和腹部神經索沒有被ARMS減少所影響。然而，我們發現三齡幼蟲晚期，其周邊神經系統中的第四級樹突分枝神經元的ddaC，和控制組比較下，ARMS減少時呈現樹突複雜度降低。Sholl氏分析和Neurolucida分析證實ARMS減少所造成的樹突複雜度降低是由於其較高級數的樹突神經纖維分枝減少、樹突末端點的數量也減少。但是ARMS減少並不影響從神經細胞本體所長出之第一級樹突的數量與細胞本體大小。為了更進一步了解ddaC樹突複雜度降低是因為樹突發育不良還是維持不良，我們觀察了更早時期，包括二齡幼蟲中期和三齡幼蟲早至中期的ddaC。此外，我們證實在ddaC中所見到的缺陷並不是因為核醣核酸干擾失準，因為過度表現ARMS可以救回ARMS減少所造成的缺陷。 已知ARMS是ephrin/Eph受體的下游分子，包含在有絲分裂原激活蛋白激酶途徑中,也有可能包含在磷脂醯肌醇激酶(phosphoinositide 3-kinases; PI3K)途徑裡，因此我們在有ARMS被核醣核酸干擾的背景下，與變異的Eph、PI3K或 MAPK等個別做結合表現，檢視其對三齡幼蟲晚期的ddaC之樹突複雜度的影響。 | zh_TW |
| dc.description.abstract | ARMS (Ankyrin repeat-rich membrane spanning), also known as Kindins220 (kinase D-interacting substrate of 220 kDa), is an evolutionarily highly conserved gene from nematode to human. ARMS can be detected in several tissues, but is most abundantly expressed in the developing and adult neural tissues, suggesting its biological role in the nervous system. Previous studies demonstrate that ARMS is a downstream target of receptor tyrosine kinase (RTK), which signals via MAPK (mitogen-activated protein kinase) pathway for sustained MAPK phosphorylation. By this way, ARMS regulates neuronal polarity and neurite outgrowth.
To investigate ARMS role in the nervous system, we have exploited Drosophila genetics. RNAi mediated knockdown of ARMS with driven expression in the eye disc in larvae stage results in defect of drosophila ommatidia in adult fly. This finding prompts us to further dissect whether such defect occurs in earlier developmental stage. By examing photoreceptors R1-R8 of optic lobe at late-third larval stage, we do not observe any defect. We thus turn to screen mushroom body (organ for olfaction and memory storage), ventral nerve cord (for transducing and processing signaling from sensory neurons to motor neurons), and the PNS (peripheral nervous system) in the developing nervous system at late-third instar stage to search for neuronal defect affected by ARMS knockdown. The results showed that the development of mushroom body and ventral nerve cord are not influenced by ARMS knockdown. However, we found ddaC, one of the class IV da (dendritic arborization) neuron in peripheral nervous system, exhibited decreased dendritic complexity in ARMS knockdown larvae compared with that in control wild-type larvae. Sholl analysis and neurolucida analysis further highlights ARMS RNAi-mediated decreased dendritic complexity results from decreased dendritic end numbers caused by less branching in higher branching orders, but not from decreased number of trees emanating from cell body. In addition, the size of cell soma does not change in neurons with RNAi of ARMS. To further understand whether alteration in dendritic complexity is due to dysregulation in the establishment or the maintenance of ddaC dendrites, we observed ddaC at earlier stage, that is, mid-second stage and early-mid third stage. We also demonstrate that the phenotype observed in larvae ddaC is not due to off-target effect of RNAi since that overexpression of ARMS rescued the defect. Given that ARMS is the downstream of ephrin/Eph and is involved in MAPK pathway and probably in PI3K (phosphoinositide 3-kinases) pathway, we examined dendritic complexity of the third instar ddaC in the genetic background of ARMS knockdown combined with altered Eph, or PI3K, or MAPK signaling activity. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:57:28Z (GMT). No. of bitstreams: 1 ntu-100-R98444006-1.pdf: 5990745 bytes, checksum: 8cbc3bc531ae448585d5c91bf3f33208 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Abstract ………i
Abstract (Chinese) ………iii Abbreviation ………v Chapter I. Introduction Section 1. ARMS ………1 Section 2. ARMS in neuron differentiation ………1 2.1. The distribution of ARMS transcripts ………1 2.2. ARMS regulates dendritic branching and spine stability ………1 2.3. ARMS regulates the establishment of neuronal polarity and Development ………2 Section 3. ARMS and Trks, Eph, MAPK in neuron differentiation ………3 3.1. ARMS is a downstream target of receptor tyrosine kinase (RTK) and plays a role in BDNF-induced neurite outgrowth ………3 3.2. ARMS is involved in MAPK (mitogen-activated protein kinase) pathway for sustained MAPK phosphorylation ………4 3.3. BDNF activates MAPK pathway and PI3K-Akt pathway ………5 3.4. The cooperation of Ras-MAPK and Ras-PI3K-Akt-mTOR pathways to regulate dendritic morphogenesis ………5 Section 4. Drosophila ………6 4.1. Life cycle ………6 4.2. UAS-GAL4 system ………7 4.3. Nervous systems at larvae stage ………7 (1) Optic lobe of visual system ………7 (2) Mushroom body ………8 (3) Ventral nerve cord ………8 (4) ddaC of class IV da neuron in peripheral nervous system ………8 Section 5. Preliminary Results from our Lab ………10 Chapter II. Hypothesis and Specific Aim ………11 Chapter III. Materials and Methods ………12 Chapter IV. Results ………17 Section 1. To investigate which neurons are specifically affected by ARMS knockdown during the development of nervous system in Drosophila ………17 1.1. ARMS knockdown caused no effect on axons of eye disc ………17 1.2. ARMS knockdown caused no effect on mushroom body ………19 1.3. ARMS knockdown caused no effect on ventral nerve cord ………19 1.4. ARMS knockdown resulted in reduction of dendritic complexity of ddaC neurons and tiling at late-thirs instar stage ………20 1.5. The reduction of dendrite complexity of ddaC neurons was due to the reduced number of dendrite ends and orders ………21 1.6. Dicer overexpression enhances the effect of ARMS-RNAi on decreased dendritic complexity ………22 1.7. ARMS overexpression partially rescues ARMS-RNAi mediated decrease of ddaC dendrite ………22 1.8. ARMS knockdown did not show any defect in ddaC neurons at second instar stage ………23 1.9. ARMS knockdown in ddaC neurons show mild defect at early-third instar stage ………24 Section 2. Whether ARMS is the downstream of Eph/ephrin and whether it is involved in PI3K or MAPK pathways to regulate neuronal development in Drosophila ………25 2.1. Consituitve activated PI3K suppresses ARMS-RNAi mediated defects in ddaC ………25 2.2. S6kKQ and ARMS-RNAi showed synergistic effects on dendritic morphogenesis ………25 2.3. The effect of erk loss of function (rl1) was too weak to have a conclusion………27 2.4. Eph and ARMS could be in the same pathway to regulate dendritic complexity………28 2.5. Ephrin did not affect ARMS in ddaC………28 Chapter V. Discussions ………30 Chapter VI. Conclusions and Perspectives ………38 References ………40 Figures ………45 Tables ………78 Figures Figure 1. ARMS knockdown is confirmed by RT-PCR ………45 Figure 2. ARMS knockdown causes no effect on axons of eye disc ………46 Figure 3. ARMS knockdown causes no effect on mushroom body ………48 Figure 4. ARMS knockdown causes no effect on ventral nerve cord ………49 Figure 5-1. ARMS knockdown results in the reduction of dendritic branching of ddaC at late-third instar stage ………50 Figure 5-2. ARMS knockdown results in the reduction of dendritic complexity of ddaC and the reduction of dendritic complexity of ddaC neurons is due to the reduced number of dendrite ends and orders ………51 Figure 6. ARMS knockdown results in the reduction of tiling at late-third instar stage ………53 Figure 7. Dicer overexpression enhances the effect of ARMS-RNAi on decreased dendritic complexity ………54 Figure 8. ARMS overexpression partially rescues ARMS-RNAi mediated decrease of ddaC dendrite ………56 Figure 9. ARMS knockdown do not show any defect in ddaC neurons at second instar stage ………59 Figure 10. ARMS knockdown in ddaC neurons show mild defect at early-third instar stage ………61 Figure 11. Consituitve activated PI3K suppresses ARMS-RNAi mediated defects in ddaC ………63 Figure 12. S6kKQ and ARMS-RNAi show synergistic effects on dendritic morphogenesis ………66 Figure 13. The effect of erk loss of function (rl1) was too weak to have a conclusion………69 Figure 14. Eph and ARMS could be in the same pathway to regulate dendritic complexity ………72 Figure 15. Ephrin did not affect ARMS in ddaC ………75 Tables Table 1. List of fly stocks ………78 Table 2. Primers for RT-PCR ………80 | |
| dc.language.iso | en | |
| dc.subject | 磷脂醯肌醇激酶 | zh_TW |
| dc.subject | 果蠅 | zh_TW |
| dc.subject | 樹突複雜度 | zh_TW |
| dc.subject | 富含連續性錨蛋白穿膜構造 | zh_TW |
| dc.subject | 絲裂原活化蛋白激酶 | zh_TW |
| dc.subject | 背部樹枝狀樹突C | zh_TW |
| dc.subject | ddaC | en |
| dc.subject | Ephrin | en |
| dc.subject | Eph | en |
| dc.subject | MAPK | en |
| dc.subject | PI3K | en |
| dc.subject | ARMS | en |
| dc.subject | Drosophila | en |
| dc.subject | dendritic complexity | en |
| dc.title | 利用果蠅遺傳學探討ARMS在神經系統發育中的功能 | zh_TW |
| dc.title | Exploration of ARMS function in the development of nervous system using Drosophila genetics | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 李秀香(Hsiu-Hsiang Lee) | |
| dc.contributor.oralexamcommittee | 吳君泰(June-Tai Wu),皮海薇(Hai-Wei Pi) | |
| dc.subject.keyword | 富含連續性錨蛋白穿膜構造,果蠅,背部樹枝狀樹突C,樹突複雜度,磷脂醯肌醇激酶,絲裂原活化蛋白激酶, | zh_TW |
| dc.subject.keyword | ARMS,Drosophila,ddaC,dendritic complexity,PI3K,MAPK,Eph,Ephrin, | en |
| dc.relation.page | 80 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-10 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
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