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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48716

Title: HIF2 alpha和NeuroD在斑馬魚胰臟Beta細胞分化過程中的功能
Functions of HIF2 alpha and NeuroD in Zebrafish Pancreatic Beta-Cell Differentiation
Authors: Chan, Shun-Hung
詹蕣璜
Contributors: 國立臺灣海洋大學:生命科學暨生物科技學系
Keywords: 斑馬魚;胰臟;低氧誘發蛋白;NeuroD;β cell
NeuroD;CNS;pancreas;zebrafish;β cell
Date: 2014
Issue Date: 2018-08-22T06:30:40Z
Abstract: NeuroD是一種具有basic helix-loop-helix(bHLH)結構的基因轉錄子,對於胚胎發育來說是很重要的,主要表現在大腦、胰臟和腸內分泌細胞中。在胚胎發育的過程中神經的分化、眼球的發育和胰臟的發育過程,都需要NeuroD的參予。在爪蟾胚胎中大量表現neurod時會出現神經元提早分化的現象,在人類中胰臟的Neurod突變會引起MODY6糖尿病。在胰臟發育過程中,分泌胰島素的β cell發育需要NeuroD參與細胞分化的工作。在另一方面,先前的研究中發現低氧誘發蛋白(HIFs)在斑馬魚神經發育的過程中會調控神經前驅細胞內的neurod,當hif2α被弱化後會抑制neurod的表現,進而造成神經發育和眼球的問題,但是目前為止尚不清楚HIF2α或是其他HIFα低氧誘發蛋白對胰臟β cell內neurod基因的影響。在本實驗中,主要是利用RNA原位雜交的方式探討斑馬魚胚胎內胰臟發育過程中hif和neurod基因間的互動關係。實驗結果顯示HIF2α或是其他HIFα並未參與胰臟β cell內neurod基因的調控,且不影響胰臟β cell的發育。此外將HIF2α的下游基因birc5a弱化,僅抑制神經細胞內的neurod的表現,但不影響胰臟細胞內的neurod的表現,顯示neurod基因的表現在不同細胞內有不同的調控機制。
NeuroD is a basic helix-loop-helix (bHLH) transcription factor that plays important roles in vertebrate CNS, retina and pancreas development. Overexpression of neurod in in Xenopus embryos induces early neuronal differentiation. Patients with Neurod mutation suffer MODY6 diabete syndrome due to dysfunctional pancreas. The pancreas β cell development is mediated by NeuroD. Previous studies demonstrated that HIF2α plays critical functions in CNS development. Depletion of HIF2α inhibited neurod expression and aboragged neuronal differentiation due to loss of birc5a expression. It is unclear whether neurod expression in pancreas β cell is also mediated by HIF2α. Here I demonstrated that the neurod expression in pancreatic cells is not mediated by HIF2α. Depletion of HIF2α did not prevent neurod transcription in pancreas cells. Furthermore, hif2α knockdown did not inbite insulin transcription in pancreas β cell. Conversely, most of neurod transcription in CNS regions was inhibited in hif2α morphants. In conclusion, this study demonstrated the neurod gene is regulated by different mechanism in neural cells and pancreas β cell.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010136037.id
http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48716
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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