| 摘要 | 第3-6页 |
| Abstract | 第6-8页 |
| CHAPTER Ⅰ A Brief Review: Cardiac chamber development and protein prenylation | 第12-57页 |
| 1.1 An overview of heart organogenesis | 第13-14页 |
| 1.2 Major cell types in the cardiac chamber | 第14-17页 |
| 1.2.1 Myocardium | 第14-16页 |
| 1.2.2 Endocardium | 第16-17页 |
| 1.2.3 Epicardium | 第17页 |
| 1.3 Cardiac chamber maturation | 第17-40页 |
| 1.3.1 Cardiac trabecualtion | 第19-20页 |
| 1.3.2 The regulation of cardiac trabeculation | 第20-25页 |
| 1.3.3 Conduction system development | 第25-28页 |
| 1.3.4 Myocardial proliferation in the compact layer | 第28-34页 |
| 1.3.5 Cardiac cytoarchitecture and its role in the cardiac chamber development | 第34-40页 |
| 1.4 Mevalonate pathway and protein prenylation | 第40-44页 |
| 1.4.1 Mevalonate pathway | 第40-42页 |
| 1.4.2 Protein prenylation | 第42-44页 |
| 1.5 The role of protein prenylation in the heart diseases and development | 第44-45页 |
| 1.6 References | 第45-57页 |
| CHAPTER Ⅱ The expression of Ggpps is augmented in mouse hearts during mid-gestation | 第57-72页 |
| 2.1 Introduction | 第58页 |
| 2.2 Materials and methods | 第58-63页 |
| 2.2.1 Mice | 第58-59页 |
| 2.2.2 Genotyping | 第59-60页 |
| 2.2.3 Immunohistochemistry and Immunofluorescence staining | 第60-61页 |
| 2.2.4 RNA extraction and Quantitative PCR | 第61-62页 |
| 2.2.5 Immunoblot analysis | 第62页 |
| 2.2.6 Cell culture | 第62页 |
| 2.2.7 Statistics analysis | 第62-63页 |
| 2.3 Results | 第63-69页 |
| 2.3.1 The expression of Ggpps increased in a stage-dependent manner in the developingheart | 第63-65页 |
| 2.3.2 Expression pattern of Nkx2~(Cre/+) and α-SMA-Cre lines | 第65-69页 |
| 2.4 Summary | 第69-70页 |
| 2.5 Discussion | 第70-71页 |
| 2.6 References | 第71-72页 |
| CHAPTER Ⅲ Protein geranylgeranylation is stage-dependently required for mammalian heart developmen | 第72-101页 |
| 3.1 Introduction | 第73-74页 |
| 3.2 Materials and methods | 第74-77页 |
| 3.2.1 Mice | 第74页 |
| 3.2.2 Genotyping | 第74页 |
| 3.2.3 Histological analysis, immunohistochemistry and immunofluorescence staining | 第74-75页 |
| 3.2.4 RNA extraction and Quantitative PCR | 第75页 |
| 3.2.5 Immunoblot analysis | 第75页 |
| 3.2.6 Tunel assay | 第75-76页 |
| 3.2.7 Primary epicardial cells culture and immunofluorescence | 第76页 |
| 3.2.8 Statistics analysis | 第76-77页 |
| 3.3 Results | 第77-94页 |
| 3.3.1 Cardiac inactivation of Ggpps by Nkx2.5~(Cre/+) resulted in mid-gestational lethality | 第77-78页 |
| 3.3.2 Cardiac inactivation of Ggpps by Nkx2.5(Cre/+) disrupted heart development during mid-gestation | 第78-91页 |
| 3.3.2.1 Cardiac inactivation of Ggpps by Nkx2.5~(Cre/-) arrested heart growth duringmid-gestation | 第78-80页 |
| 3.3.2.2 Cardiac inactivation of Ggpps by Nkx2.5~(Cre/-) resulted in aberrant myocardialproliferation, but had no effects on myocardial apoptosis | 第80-83页 |
| 3.3.2.3 Cardiac inactivation of Ggpps by Nkx2.5~(Cre/-) resulted in the abnormaltrabecular regional specification | 第83-86页 |
| 3.3.2.4 Cardiac inactivation of Ggpps by Nkx2.5~(Cre/-) caused abnormal epicardiumdevelopment | 第86-91页 |
| 3.3.3 Later cardiac inactivation of Ggpps by α-SMA-Cre did not affect embryonic heart development | 第91-94页 |
| 3.4 Summary | 第94-95页 |
| 3.5 Discussion | 第95-98页 |
| 3.6 References | 第98-101页 |
| CHAPTER Ⅳ Protein geranylgeranylation regulates the organization of cardiomyocytes through modulating RhoGTPase activity | 第101-124页 |
| 4.1 Introduction | 第102-103页 |
| 4.2 Materials and methods | 第103-106页 |
| 4.2.1 Mice | 第103页 |
| 4.2.2 Histological analysis, immunohistochemistry and immunofluorescence staining | 第103页 |
| 4.2.3 WGA staining | 第103页 |
| 4.2.4 Transmission electron microscopy | 第103-104页 |
| 4.2.5 Immunoblot analysis | 第104页 |
| 4.2.6 Immunoprecipitation analysis | 第104页 |
| 4.2.7 RNA extraction and Quantitative PCR | 第104页 |
| 4.2.8 Cell culture | 第104-105页 |
| 4.2.9 Triton X-114 extraction of hydrophobic proteins | 第105-106页 |
| 4.2.10 Small GTPase activity assay | 第106页 |
| 4.2.11 Statistical analysis | 第106页 |
| 4.3 Results | 第106-117页 |
| 4.3.1 Mid-gestational disruption of protein geranylgeranylation led to the disorganization ofcardiac cytoarchitecture | 第106-108页 |
| 4.3.2 Protein geranylgeranylation was essential for cell-cell junctions in cardiomyocytesduring mid-gestation | 第108-113页 |
| 4.3.3 Mid-gestational disruption of protein geranylgeranylation disturbed cardiaccytoarchitectural establishment by inhibiting Rho GTP ases activity | 第113-117页 |
| 4.4 Summary | 第117页 |
| 4.5 Discussion | 第117-121页 |
| 4.6 References | 第121-124页 |
| Appendix | 第124-127页 |
| 致谢 | 第127-128页 |
| Publication | 第128-130页 |
