| Abstract | 第1-8页 |
| 中文摘要 | 第8-10页 |
| List of Abbreviation | 第10-12页 |
| PART 1:Reviews | 第12-46页 |
| Review 1:Signaling Regulation in Heart Development | 第13-27页 |
| Table of content | 第13-14页 |
| 1. Introduction | 第14-16页 |
| 2. Heart development program | 第16-21页 |
| ·Specification and induction of cardiac progenitor cells | 第16-19页 |
| ·Formation of heart tube | 第19页 |
| ·Left-right asymmetry and cardiac looping | 第19-20页 |
| ·Chamber formation,maturation,septation,and growth | 第20-21页 |
| 3. Summary of the heart development | 第21-22页 |
| 4. Future Perspectives and open questions | 第22-24页 |
| 5. References | 第24-27页 |
| Review 2:PKB/Akt signaling in cardiac development and disease | 第27-46页 |
| Table of content | 第27-28页 |
| Abstract | 第28页 |
| 1. Introduction | 第28-32页 |
| 2. Akt signaling in heart development and disease | 第32-37页 |
| ·Akt signaling in heart development | 第32-33页 |
| ·Akt signaling in cardiac remodeling and disease | 第33-36页 |
| ·Akt signaling in cardiac protection | 第36-37页 |
| 3. Conclusion and perspective | 第37-41页 |
| 4. References | 第41-46页 |
| PART 2:The role of Akt isoforms in the heart development | 第46-87页 |
| Chapter 1:Deletion of Akt1 causes heart defects and abnormalcardiomyocyte proliferation | 第47-73页 |
| Table of content | 第47-48页 |
| Abstract | 第48-49页 |
| 1. Introduction | 第49-50页 |
| 2. Materials and methods | 第50-53页 |
| ·Mice and animal care | 第50页 |
| ·Genotyping | 第50-51页 |
| ·Hematoxylin-eosin(HE)and immunofluorescence(IF)staining | 第51页 |
| ·BrdU incorporation assay | 第51页 |
| ·Cell culture | 第51-52页 |
| ·Western blotting analysis and antibodies | 第52-53页 |
| ·Echocardiography(Echo) | 第53页 |
| ·Statistical analysis | 第53页 |
| 3. Results | 第53-68页 |
| ·Akt1 is the dominant isoform in the heart | 第53-54页 |
| ·Akt1 mutant mice displayed higher post—natal mortality on the background of C57BL/6J | 第54-55页 |
| ·Akt1 mutant mice displayed heart defects,impaired heart function | 第55-59页 |
| ·Decreased cell proliferation and capillary density in Akt1 deficient heart | 第59-62页 |
| ·Substantial activation of p38MAPK signaling pathway in Akt1-deficient heart | 第62-65页 |
| ·Haploinsufficiency of p38α partially rescues post-natal mortality and frequency of heart defects in Akt1 nulls mice | 第65-68页 |
| 4. Discussion | 第68-71页 |
| 5. References | 第71-73页 |
| Chapter 2:Establishment of Akt1 floxed mice and study of compoundknockout Akt1,and Akt3 mice in heart development | 第73-85页 |
| Table of content | 第73-74页 |
| 1. Introduction | 第74页 |
| 2. Materials and methods | 第74-77页 |
| ·Generation and characterization of mice with a conditional-targeted Akt1 allele | 第74-75页 |
| ·Mice and animal care | 第75页 |
| ·Genotyping | 第75-76页 |
| ·Hematoxylin-eosin(HE)and immunofluorescence(IF)staining | 第76-77页 |
| ·Western blotting analysis and antibodies | 第77页 |
| 3. Results | 第77-85页 |
| ·Establishment of Akt1 floxed mice | 第77-79页 |
| ·Partial cardiac specific knockout of Akt1 mice show heart defects | 第79-81页 |
| ·Cardiac specific knockout of Akt1 mice show normal natality | 第81-82页 |
| ·Gene dosage regulation of Akt1 and Akt3 in the heart development | 第82-83页 |
| ·The Akt1~(F/F);Mesp1-Cre~(+/-);Akt3~(homo) mice show obvious heart development | 第83-84页 |
| ·Decreased cell proliferation in hearts of Mesp1-cre-mediated cardiac specific combined knockout of Akt1 and Akt3 mice | 第84-85页 |
| 4. Discussion | 第85-86页 |
| 5. References | 第86-87页 |
| Acknowledgements | 第87-88页 |
| Publication | 第88-90页 |
