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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58765
標題: | Nogo/Nogo接受器複合體在斑馬魚側線發育之功能性分析 Functional studies of Nogo/Nogo receptor complex in zebrafish lateral line development |
作者: | Hao-Wei Han 韓皓偉 |
指導教授: | 黃銓珍 |
關鍵字: | Nogo接受器複合體,神經丘,側線原基質,側線,斑馬魚, Nogo-C2/Nogo receptor complex,p75,TROY,neuromast,primordium,lateral line,zebrafish, |
出版年 : | 2013 |
學位: | 博士 |
摘要: | The fish lateral line (LL) is a mechanosensory system closely related to the hearing system of higher vertebrates, and it is composed of several neuromasts located on the surface of the fish. These neuromasts can detect changes in external water flow, to assist fish in maintaining a stationary position in a stream. In the present study, we identified a novel function of Nogo/Nogo receptor signaling in the formation of zebrafish neuromasts. Nogo signaling in zebrafish, like that in mammals, involves three ligands and four receptors, as well as three co-receptors (TROY, p75, and LINGO-1). We first demonstrated that Nogo-C2, NgRH1a, p75, and TROY are able to form a Nogo-C2 complex, and that disintegration of this complex causes defective neuromast formation in zebrafish. Time-lapse recording of the CldnB::lynEGFP transgenic line revealed that functional obstruction of the Nogo-C2 complex causes disordered morphogenesis, and reduces rosette formation in the posterior LL (PLL) primordium during migration. Consistent with these findings, hair-cell progenitors were lost from the PLL primordium in p75, TROY, and Nogo-C2/NgRH1a morphants. Notably, the expression levels of pea3, a downstream marker of Fgf signaling, and dkk1b, a Wnt signaling inhibitor, were both decreased in p75, TROY, and Nogo-C2/NgRH1a morphants; moreover, dkk1b mRNA injection could rescue the defects in neuromast formation resulting from knockdown of p75 or TROY. We thus suggest that a novel Nogo-C2 complex, consisting of Nogo-C2, NgRH1a, p75, and TROY, regulates Fgf signaling and dkk1b expression, thereby ensuring stable organization of the PLL primordium.
In addition, we also demonstrated that the neuromast formation was abolished in embryos treated with HDAC inhibitors, OSU-HDAC42 and trichostatin A, and the respective expression of Nogo-C2, NgRH1a, p75 and TROY was down-regulated in these embryos. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58765 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科學研究所 |
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