| Abstract | 第1-6页 |
| 摘要 | 第6-8页 |
| Index | 第8-10页 |
| 1. Introduction | 第10-30页 |
| ·RING finger proteins | 第10-13页 |
| ·Structure of RING domain | 第10页 |
| ·Biological functions of RING proteins | 第10-13页 |
| ·RING finger protein 10 | 第13-15页 |
| ·Rnf10 protein structure | 第13-14页 |
| ·Rnf10 gene structure | 第14页 |
| ·Rnf10 functional background | 第14-15页 |
| ·Neuronal differentiation and neural fate determination | 第15-28页 |
| ·Restriction points in neural fate determination | 第16-17页 |
| ·Major signalling pathways in neural fate determination | 第17-19页 |
| ·Interplay between Cell cycle and neural fate determination | 第19-28页 |
| ·Cell cycle phases and neural fate determination | 第19-23页 |
| ·Role of Cyclin dependent kinases in neuronal differentiation | 第23-25页 |
| ·Role of Cyclin dependent kinase inhibitors in neuronal differentiation | 第25-28页 |
| ·Objectives of study | 第28-30页 |
| 2. Materials and methods | 第30-34页 |
| ·Antibodies | 第30页 |
| ·Cell culture and differentiation | 第30-31页 |
| ·Real-time quantitative PCR analysis | 第31页 |
| ·Western blot analysis | 第31-32页 |
| ·Cell transfections and transductions | 第32页 |
| ·Immunocytochemistry | 第32-33页 |
| ·Flow cytometry analysis of cell cycle distribution | 第33页 |
| ·Cell proliferation assays | 第33页 |
| ·Cell toxicity and cell death assays | 第33页 |
| ·Statistical analysis | 第33-34页 |
| 3. Results | 第34-49页 |
| ·RING finger protein 10 regulates retinoic acid-induced neuronal differentiation and the cell cycle exit of P19 embryonic carcinoma cells | 第34-46页 |
| ·Differentiation of P19 cells in serum free conditions | 第34页 |
| ·Expression of Rnf10 during P19 cell neuronal differentiation, in cerebellar granular cells and in areas of the mouse brain | 第34-38页 |
| ·Rnf10 knockdown results in the impaired neuronal differentiation of P19-derived neurons | 第38-40页 |
| ·Effect of Rnf10 depletion on the cell cycle profile, cell proliferation and cyclin-dependent kinase inhibitors | 第40-43页 |
| ·The effect of p21 knockdown was similar to Rnf10 depletion, and its overexpression can partially rescue neuronal differentiation in Rnf10 knockdown cells | 第43-46页 |
| ·Doxycycline pre-treatment can reduce cell apoptosis and cell toxicity in neural stem cells under oxidative stress | 第46-49页 |
| 4. Discussion | 第49-53页 |
| ·Rnf10 is extensively expressed in mouse brain and neuronal subtypes and regulates neuronal differentiation | 第49-50页 |
| ·Rnf10 mediates cell cycle exit and the expression of cyclin kinase inhibitor p21 | 第50-51页 |
| ·Rnf10 regulates neuronal differentiation through p21 pathway | 第51页 |
| ·Doxycycline pre-conditioning provides cytoprotection to neural stem cells under oxidative stress | 第51-53页 |
| Conclusions and Future prospects | 第53-54页 |
| References | 第54-68页 |
| Acknowledgments | 第68-69页 |
| Publications | 第69页 |
