Paxillin在脊髓運動神經軸突引導中的作用

Taipei Medical University Institutional Repository > 醫學科技學院 > 神經再生醫學博士學位學程 > 博碩士論文 > Item 987654321/61326

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題名:	Paxillin在脊髓運動神經軸突引導中的作用 Paxillin function in spinal motor axon guidance
作者:	蔡宛玲 TSAI, WAN-LING
貢獻者:	神經再生醫學博士學位學程高祖仁葉修華
關鍵詞:	paxillin;軸突引導;運動神經元;脊髓 paxillin;axon guidance;motor neuron;spinal cord
日期:	2021-06-28
上傳時間:	2022-01-24 17:56:53 (UTC+8)
摘要:	神經與神經之間的連結如果產生了錯誤的連結，有可能會導致智能發展障礙或癲癇等相關疾病。但是，到目前為止，對於神經是如何形成正確而精準連結的機制還是不甚了解。為了克服研究神經系統時常遇到的神經網絡高複雜性的問題，我利用一個構造比較簡單的部位去作相關的研究:脊髓外側運動神經柱(lateral motor column, LMC)的運動神經元會生長至肢體肌肉組織，在發育的過程中會作出兩個主要的路徑選擇。位於脊髓側邊部位的LMC運動神經軸突會選擇往背側肢體肌肉生長，而脊髓中間部位的LMC運動神經軸突會往腹側肢體肌肉作延伸。Eph和ephrin所產生的排斥訊息對於LMC軸突的正確路徑選擇是非常重要的。但是，Eph/ephrin所產生訊息的機制及負責訊息傳遞的中間物質到目前為止還不是很清楚。其中一種可能負責Eph訊息傳遞的中間物質是paxillin，一種focal adhesion轉接蛋白，它被認為可能在中樞神經系統的細胞發育過程中有一些重要的功能。依據這些觀察，我們提出以下的假設: 在LMC神經元中，paxillin的功能是傳遞Eph訊息的重要中間物質，讓LMC軸突能正確地生長到肢體肌肉。利用原位雜合技術，我們首先確認了paxillin在雞及小鼠胚胎LMC部位的表達。接著我們利用雞胚胎電穿孔技術發現，過度與抑制paxillin表達均會造成LMC運動神經的錯誤引導。並透過離體實驗去進一步確認，paxillin在LMC中是否為傳遞Eph訊息的重要中間物質。依據實驗結果，我們發現：1. Paxillin在小鼠及雞胚胎脊髓運動神經軸突生長至肌肉組織的時期，其在LMC神經元中有明顯的表達。2. Paxillin的功能是傳遞Eph訊息的重要中間物質，其作用是讓LMC軸突能正確的選擇其該往哪側肌肉做為生長方向。3.Paxillin在Eph的訊息傳遞過程中，可能和Src和ephexin-1有交互影響的作用。本論文的結論為，Paxillin在運動神經軸突生長過程中是必需的中間物質，而且在ephrin:Eph的訊號傳遞過程中，扮演重要的角色。 Defects in neuronal connectivity can lead to mental retardation and disorders such as epilepsy, but how precise neuronal connections form is still poorly understood. To circumvent the problem of nervous system complexity, I study a simple binary axon pathfinding choice made by spinal lateral motor column (LMC) motor axons projecting to the base of the limb. Lateral LMC motor axons invariantly project towards dorsal limb musculature whereas medial LMC motor axons invariantly project towards the ventral limb. Repulsive Eph/ephrin signaling is essential for the proper trajectory of LMC axons. However, the underlying mechanism of Eph/ephrin signaling at this context is still unclear. One candidate molecule to function as intermediates of Eph signaling is a focal adhesion adaptor protein, paxillin, which has been suggested to involve in several cellular events of developing central nervous system, prompting us to dissect its function in LMC axon guidance. Using the in situ hybridization technique, we first identified the expression of paxillin mRNA in most LMC neurons of both mouse and chick embryos at the relevant stages. We then demonstrated that both paxilin knockdown and overexpression using the in ovo electroporation induced motor axon pathfinding mistakes, we also demonstrate that knocking down paxillin lower the repulsion effect of neurites of culture LMC explants against ephrins, suggesting the essential role of paxillin in the proper LMC axon trajectory into the limb. In summary, we demonstrate that: 1. paxillin is obviously expressed in LMC neurons when mice and chicken embryonic spinal motor axons grow into the limb muscle; 2. paxillin functions as an important intermediate that transmits Eph signaling, and its role in the ephrin:Eph signaling pathway resuls in motor axon trajectory selection; 3. paxillin may interact with Src and ephexin-1 during ephrin:Eph signaling pathway. In conclusion, we show that paxillin is involved in the proper trajectory of spinal motor axons and plays an important role in the ephrin:Eph signaling pathway in this context.
描述:	博士指導教授：高祖仁指導教授：葉修華委員：李宜釗委員：王培育委員：莊健盈
資料類型:	thesis
顯示於類別:	[神經再生醫學博士學位學程] 博碩士論文

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