Abstract | 第5-7页 |
中文摘要 | 第8-10页 |
Abbreviations | 第10-12页 |
Chapter 1: Review | 第12-49页 |
1.1 Actin dynamics | 第13-21页 |
1.1.1 Actin in mammalian cells | 第13-16页 |
1.1.2 Actin dynamics is regulated by actin-binding proteins | 第16-19页 |
1.1.3 ADF/cofilin | 第19-21页 |
1.2 WDR1 actively disassembles ADF/cofilin-bound actin filaments | 第21-25页 |
1.2.1 Biochemical properties of WDR1 | 第21-23页 |
1.2.2 Functions of WDR1 | 第23-25页 |
1.3 Actin dynamics in muscle cells and congenital myopathies | 第25-29页 |
1.3.1 Actin dynamics in striated muscle cells | 第25-27页 |
1.3.2 Regulators of actin dynamics in striated muscle | 第27-29页 |
1.3.3 Actin dynamics deregulation and congenital myopathies | 第29页 |
1.4 Mouse heart development | 第29-33页 |
1.4.1 Basic heart development | 第30-32页 |
1.4.2 The first heart field (FHF) and the second heart field (SHF) | 第32-33页 |
1.5 SHF progenitor cells behavior and actin dynamics | 第33-40页 |
1.5.1 The discovery of the SHF | 第33-35页 |
1.5.2 The properties of the SHF | 第35-38页 |
1.5.3 SHF progenitor cells behavior regulation and actin dynamics | 第38-40页 |
References | 第40-49页 |
Chapter 2: WDR1 plays essential functional roles for actin disassembly duringmyocardial growth and maintenance in mice | 第49-78页 |
Summary | 第50页 |
Results | 第50-67页 |
2.1 Generation of cardiomyocyte-specific Wdr1 deletion mice | 第50-53页 |
2.2 Wdr1 deficient mice displayed early lethality, heart hypertrophy and impaired heartcontraction function | 第53-55页 |
2.3 Wdr1 cKO mice showed prolonged QT and increased ST height, T -wave amplitude | 第55-57页 |
2.4 F-actin accumulations in the myocardium of Wdr1 deficient mice | 第57-59页 |
2.5 Cardiac muscles in Wdr1 deficient mice displayed severe disruptions of sarcomericstructure | 第59-62页 |
2.6 Increased levels of sarcomeric proteins and cofilins in the heart of Wdr1 cKO mice | 第62-64页 |
2.7 Deleting Wdr1 in adult heart also resulted in mice lethality, heart hypertrophy andF-actin accumulations within myofibrils | 第64-67页 |
Discussion | 第67-69页 |
Materials and Methods | 第69-76页 |
References | 第76-78页 |
Chapter 3: WDR1-mediated actin dynamics plays indispensible roles during theanterior second heart field progenitor cells development | 第78-101页 |
Summary | 第79-80页 |
Results | 第80-96页 |
3.1 Generation of Wdr1 knockout mice in the SHF | 第80-82页 |
3.2 Wdr1 deleted mice exhibited embryonic lethality, reduced size of the RV, and theproximal OFT | 第82-84页 |
3.3 Deficiency of Wdr1 in SHF did not impair the pool and maturation of SHFprogenitors in PM, SpM and the distal OFT | 第84-87页 |
3.4 Loss of Wdr1 did not disrupt cellular organization and polarity in the distal OFT | 第87-90页 |
3.5 The cellular arrangement, and myofibrillogenesis of sarcomeric thin filament in theproximal OFT and RV of Wdr1 shfKO embryos were seriously disrupted | 第90-96页 |
Discussion | 第96-98页 |
Materials and Methods | 第98-99页 |
References | 第99-101页 |
Publications | 第101-102页 |
致谢 | 第102-105页 |