碩士 / 國立臺灣海洋大學 / 生物科技研究所 / 99 / Abstract
Hypoxia-inducible factors (HIFs) are known for their functions in oxygen homeostasis by regulating the genes for glucose uptake and metabolism, erythorpoiesis, angiogenesis, apoptosis and cell proliferation. The HIFs are heterodimeric basic-helix-loop-helix-PAS transcription factors that consist of an oxygen-sensitive alpha subunit and a constitutively expressed beta subunit, also known as ARNT. When cells are subjected to hypoxia, the HIFα factors are stabilized, associate with ARNT and activate the target genes. NeuroD is a basic helix-loop-helix transcription factor that functions to regulate cell cycle, determine neuronal fates and control neuronal differentiation. It also acts important role in linking cell cycle withdrawal with terminal differentiation.
Previously it was revealed that zebrafish HIF2α protects neural progenitor cells and neural differentiation processes by upregulating the survivin orthologues birc5a and birc5b during embryogenesis. Concurrent knockdown of zebrafish hif2α inhibited neuroD transcription. Here I have examined the close interactions between hif2α, survivin orthologues and neuroD genes during neurogenesis.
Morpholino-mediated knockdown of hif2α, birc5a and birc5b reduced the expression of the neuroD, elavl3/HuC, cdk inhibitors p27/cdkn1b and p57/cdkn1c and increased ccnd1/cyclin D1 and pcna expression. Neuronal apoptosis was also greatly enhanced. The diminished neuroD and HuC expression observed in hif2α morphant was largely rescued by ectopic birc5a or-5b mRNAs. On the other hand, the hif2α morpholino-mediated birc5a and birc5b depletion was also greatly rescued by ectopic neuroD mRNA. Here I demonstrated that neuroD and survivin orthologues are mutually regulated under HIF2α control. This closely correlations between neuroD and survivin orthologues secure the neural progenitor cell survival and differentiation in zebrafish embryo.
| Identifer | oai:union.ndltd.org:TW/099NTOU5613017 |
| Date | January 2011 |
| Creators | Ya-Ting Chang, 張雅婷 |
| Contributors | Chin-Hwa Hu, 胡清華 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 66 |
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