Regulation of Drosophila intestinal regeneration by the Hippo pathway

............................................................................................................... 3
 Acknowledgement ............................................................................................... 4
 Table of Contents ................................................................................................ 5
 Table of figures .................................................................................................... 9
 List of tables ...................................................................................................... 11
 Abbreviations ..................................................................................................... 12
 Chapter 1.
 Introduction ................................................................................... 18
 1.1 The fruit fly as model for growth control ........................................................... 18
 1.1.1
 Drosophila melanogaster as a model organism ........................................... 18
 1.1.2
 Lifecycle of Drosophila melanogaster ......................................................... 19
 1.1.3
 Growth regulatory processes in Drosophila ................................................. 20
 1.2
 The Hippo growth regulation pathway ............................................................ 24
 1.2.1
 The Hpo pathway controls both cell cycle exit and apoptosis ...................... 24
 1.2.2
 The core kinase cascade ................................................................................ 27
 1.2.3
 The Hpo pathway is regulated by multiple inputs ........................................ 32
 1.2.4
 A highly conserved signalling pathway ........................................................ 40
 1.2.5
 Cross-talk with other pathways .................................................................... 41
 1.2.6
 Multiple functions of the Hpo pathway ........................................................ 41
 1.2.7
 Hpo signalling in stem cells and progenitor populations .............................. 42
 1.3
 Stem cells ............................................................................................................ 46
 1.3.1
 Definition of a stem cell ............................................................................... 46
 1.3.2
 The stem cell niche ....................................................................................... 46
 1.3.3
 Stem cell division and dynamics .................................................................. 47
 1.3.4
 Stem cell populations in Drosophila ............................................................ 47
 1.3.5
 Stem cells and ageing ................................................................................... 51
 1.3.6
 Cancer stem cells .......................................................................................... 52
 1.4
 The mammalian intestine .................................................................................. 52
 1.4.1
 Organisation of the intestinal epithelium ...................................................... 53
 1.4.2
 Epithelial renewal ......................................................................................... 55
 1.4.3
 Adult intestinal stem cells ............................................................................. 55
 1.4.4
 Key signalling pathways controlling intestinal crypt homeostasis ............... 57
 1.5
 The adult Drosophila posterior midgut ............................................................ 58
 1.5.1
 Structure of the Drosophila intestinal tract .................................................. 58
 1.5.2
 Development of the adult midgut ................................................................. 60
 1.5.3
 Cellular organisation of the posterior midgut ............................................... 61
 1.5.4
 The adult posterior midgut intestinal stem cell population .......................... 63
 1.5.5
 Regulation of homeostatic proliferation in the posterior midgut .................. 67
 1.5.6
 The midgut ISC niche ................................................................................... 72
 1.5.7
 The gut microbiome and immune system ..................................................... 72
 1.5.8
 The intestinal response to stress or injury ..................................................... 76
 1.6
 Aim of PhD project: A role for the Hippo pathway in the adult posterior midgut? ........................................................................................................................ 83
 Chapter 2.
 Materials & Methods .................................................................... 85
 2.1
 Drosophila manipulations and genetic techniques .......................................... 85
 2.1.1
 Techniques for generating fly stocks ............................................................ 85