請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43742
標題: | 線蟲吞噬細胞藉由 ced-5/DOCK180 促進神經再生 The engulfment cells promote axon regeneration via CED-5/DOCK180 in C. elegans |
作者: | Hui Chiu 邱卉 |
指導教授: | 吳益群(Yi-Chun Wu) |
關鍵字: | 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, C. elegans,Femtosecond laser axotomy,Axon regeneration,Engulfment,(Guanine nucleotide Exchange Factor) GEF, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | 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。 Two 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43742 |
全文授權: | 有償授權 |
顯示於系所單位: | 分子與細胞生物學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-100-1.pdf 目前未授權公開取用 | 896.68 kB | 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。