Focal Adhesion Kinase and ARHGAP26 in Cardiac and Skeletal Muscle Development

...................................................................................................................... iii ACKNOWLEDGEMENTS ................................................................................................ v TABLE OF CONTENTS ................................................................................................ viii LIST OF TABLES ............................................................................................................. xi LIST OF FIGURES...........................................................................................................xii LIST OF ABBREVIATIONS .......................................................................................... xiv INTRODUCTION ..................................................................................................................... 1 CARDIAC AND SKELETAL MUSCLE DEVELOPMENTAL DEFECTS (OVERVIEW) ...........................................................................................................1 CARDIAC DEVELOPMENT ....................................................................................................2 SKELETAL MUSCLE DEVELOPMENT ....................................................................................4 INTEGRINS AND THEIR ROLE IN DEVELOPMENT ....................................................................5 FAK COORDINATES INTEGRIN SIGNALING ..........................................................................7 GRAF IS A FAK BINDING PARTNER ......................................................................................8 RHO-FAMILY GTPASES AND THEIR REGULATION .................................................................8 INTEGRINS AND THE DYSTROPHIN-GLYCOPROTEIN COMPLEX ARE DEFECTIVE IN VARIOUS MUSCULAR DYSTROPHIES .................................................. 11 FAK IN CARDIAC AND SKELETAL MUSCLE DEVELOPMENT .................................................. 12 RHO IN CARDIAC AND SKELETAL MUSCLE DEVELOPMENT – IMPLICATIONS FOR GRAF ...................................................................................... 14 MODELS UTILIZED HEREIN ............................................................................................... 16 GOAL OF THESIS............................................................................................................... 18