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  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 分子與細胞生物學研究所
Please use this identifier to cite or link to this item: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43742
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???org.dspace.app.webui.jsptag.ItemTag.dcfield???ValueLanguage
dc.contributor.advisor吳益群(Yi-Chun Wu)
dc.contributor.authorHui Chiuen
dc.contributor.author邱卉zh_TW
dc.date.accessioned2021-06-15T02:27:24Z-
dc.date.available2013-08-20
dc.date.copyright2011-08-20
dc.date.issued2011
dc.date.submitted2011-08-17
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43742-
dc.description.abstract在模式物種線蟲 Caenorhabditis elegans 中,周邊神經受傷害之後引起兩件重要的生物性事件同時發生:軸突碎屑的產生以及神經再生的促進。過去的研究並未解釋這兩件事如何彼此調控。在這篇研究中,我們觀察發現,軸突被截斷之後的幾分鐘之內,其中尚與神經細胞本體連結的軸突會於末梢崩落出局部性的軸突碎屑。這樣只侷限分佈於受傷位置的局部性軸突碎屑並未被描述於過去的神經再生研究中,並且,它與經由瓦勒式退化所產生之軸突碎屑十分不同。瓦勒式退化所產生的軸突碎屑指的是軸突被截斷之後, 其中與神經細胞分離的那一整節軸突會於受傷的幾天之內瓦解成不連續的片段。有趣的是,我們發現局部性軸突碎屑的清除和神經再生的啟動之間有緊密的關聯性。我們推測這可能說明了局部性軸突碎屑的清除是啟動神經再生的必要前置作業,或者,吞噬細胞在清除局部性軸突碎屑的過程中也能夠同時促進神經再生。過去在不同物種的研究中已經指出吞噬細胞清除軸突碎屑的過程是可能受到吞噬基因的調控。我們的研究結果發現吞噬基因也參與了神經再生的調控。若吞噬基因之一的鳥嘌呤轉換因子 CED-5/DOCK180 發生突變會抑制線蟲的神經再生能力。於 ced-5 突變蟲體中,當正常功能的 CED-5 藉由細胞專一表現啟動子特定表現在神經細胞內部或包含了體壁肌肉在內的三種吞噬細胞中可以恢復神經再生的能力。本篇研究結果顯示了線蟲的體壁細胞是如何藉由鳥嘌呤轉換因子 ced-5 的作用促進神經再生。zh_TW
dc.description.abstractTwo important biological events happen coincidently after axon injury in the PNS neurons of Caenorhabditis elegans. One is the generation of axon debris and the other is the promotion of axon regeneration. It is not known how these two events are regulated and related to each other. In this report, we observed a local shedding of the axon debris from the proximal end of the severed axon within minutes after axon injury. This type of axon debris is previously undescribed and distinctive from the axon debris generated by Wallerian degeneration, which is the distal segment of the severed axon becomes globally fragmented within days after axon injury. Interestingly, the removal of the proximal-end axon debris appears to coincide with the initiation of axon regeneration. We reasoned that either the removal of the proximal-end axon debris is a prerequisite for initiating axon regeneration or the engulfment cells required for removing axon debris is also utilized for promoting axon regeneration. Our results suggested that CED-5/DOCK180 guanine nucleotide exchange factor plays an important role in regulating axon regeneration since mutations in ced-5 caused significantly reduced axon regeneration. Furthermore, cell specific rescue experiments showed that expression of ced-5 in either the touch neurons or another three types of somatic cells fully rescued the defective axon regeneration phenotypes in ced-5 mutants. Thus, our study revealed the cell autonomous and non-cell autonomous roles of ced-5 in axon regeneration.en
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dc.description.tableofcontents論文口試委員審定書
中文摘要 i
Abstract ii
Table of Contents iii
I. Introduction 1
1.1 C. elegans as a genetic model to identify novel cellular and molecular mechanisms underlying nervous system regeneration 1
1.2 The canonical pathways involved in the engulfment of apoptotic cells 13
II. Materials and methods 16
2.1 Strains 16
2.2 The creation of transgenic animals 16
2.3 Microscopy 16
2.4 Femtosecond laser surgery 17
2.5 Measuring regenerative axon length 17
2.6 Plasmid construction 18
III. Results 20
3.1 The initiation of axon regeneration is associated with the disappearance of axon debris 20
3.2 The differential roles of engulfment genes in axon regeneration 21
3.3 ced-5 functions both cell autonomously in the touch neurons and non-cell autonomously in multiple types of cells to affect ALM axon regeneration 21
IV. Discussion 23
4.1 The discovery of the extrinsic factors that promote axon regeneration 23
V. Reference 24
VI. Figures 31
Figure 1. Analogous counterparts of the human nervous systems in C. elegans 31
Figure 2. Study of axon regeneration using femtosecond laser axotomy and live imaging 33
Figure 3. The axon debris accumulation is tightly linked with the axon regeneration initiation 35
Figure 4. Selective engulfment genes are essential for axon regeneration 37
Figure 5. The expression pattern of a 1.3-Kb ced-5 promoter::GFP reporter in the adult animals 44
Figure 6. ced-5 has both cell autonomous and non-cell autonomous roles in regulating ALM axon regeneration 41
VII. Tables 43
7.1 The conserved patterns and molecular mechanisms of axon regeneration between vertebrates and C. elegans 43
7.2 The list of the transgenes used in this study 44
dc.language.isoen
dc.subject鳥嘌呤轉換因子zh_TW
dc.subject線蟲zh_TW
dc.subject飛秒雷射軸突截斷技術zh_TW
dc.subject神經再生zh_TW
dc.subject吞噬作用zh_TW
dc.subjectFemtosecond laser axotomyen
dc.subjectC. elegansen
dc.subject(Guanine nucleotide Exchange Factor) GEFen
dc.subjectEngulfmenten
dc.subjectAxon regenerationen
dc.title線蟲吞噬細胞藉由 ced-5/DOCK180 促進神經再生zh_TW
dc.titleThe engulfment cells promote axon regeneration via CED-5/DOCK180 in C. elegansen
dc.typeThesis
dc.date.schoolyear99-2
dc.description.degree碩士
dc.contributor.coadvisor掌杰(Chieh Chang)
dc.contributor.oralexamcommittee莊秋芬(Chiou-Fen Chuang),張俊哲(Chun-Che Chang),廖秀娟(Hsiu-Chuan Liao),潘俊良(Chun-Liang Pan)
dc.subject.keyword線蟲,飛秒雷射軸突截斷技術,神經再生,吞噬作用,鳥嘌呤轉換因子,zh_TW
dc.subject.keywordC. elegans,Femtosecond laser axotomy,Axon regeneration,Engulfment,(Guanine nucleotide Exchange Factor) GEF,en
dc.relation.page46
dc.rights.note有償授權
dc.date.accepted2011-08-17
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept分子與細胞生物學研究所zh_TW
Appears in Collections:分子與細胞生物學研究所

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