This document contains a full summary from all the lectures Molecular Developmental Biology, as well as some background and extra information from the book to fully grasp each topic.
Dit bestand bevat een volledige samenvatting van alle behandelde hoofdstukken en hun repectivelijk deel uit het han...
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,H0: OVERVIEW OF THE COURSE ......................................................................................................................................... 1
LEARNING OUTCOMES – 5 CREDITS ......................................................................................................................................... 1
COURSE CONTENT ............................................................................................................................................................... 1
THE EXAM ......................................................................................................................................................................... 1
H1: FRAMEWORK TO UNDERSTAND DEVELOPMENT ......................................................................................................... 2
1.1 A GENERAL INTRODUCTION .............................................................................................................................................. 2
1.1.1 What is development? ...................................................................................................................................... 2
1.1.2 How are you, you? ............................................................................................................................................ 2
1.1.3 The circle of life ................................................................................................................................................. 4
1.2 HISTORY OF DEVELOPMENTAL RESEARCH ............................................................................................................................. 7
1.2.1 What happens: anatomy and embryology ........................................................................................................ 7
1.2.2 What drives embryogenesis: experimental embryology & developmental biology ............................................. 9
1.2.3 What is the molecular basis: molecular developmental biology ...................................................................... 12
1.2.4 Are molecules, pathways, principles conserved: Evo-Devo............................................................................... 12
1.3 CELL-TO-CELL COMMUNICATION ..................................................................................................................................... 13
1.3.1 A primer on cell-to-cell communication ........................................................................................................... 13
1.3.2 Adhesion and sorting: juxtacrine signalling ..................................................................................................... 14
1.3.3 The epithelial-mesenchymal transition (EMT) ................................................................................................. 15
1.3.4 Paracrine factors: inducer molecules ............................................................................................................... 15
1.3.5 Juxtacrine signalling for cell identity................................................................................................................ 19
1.4 ABNORMAL DEVELOPMENT............................................................................................................................................ 20
1.4.1 Genetic malformations and syndromes ........................................................................................................... 20
1.4.2 Disruptions and teratogens ............................................................................................................................. 20
1.5 GENE REGULATION IN DEVELOPMENT ............................................................................................................................... 21
1.5.1 Defining differential gene expression .............................................................................................................. 21
1.5.2 Central dogma ................................................................................................................................................ 21
1.5.3 Evidence for genomic equivalence ................................................................................................................... 22
1.5.4 Anatomy of the gene (background) ................................................................................................................. 22
1.5.5 Mechanisms of differential gene expression: transcription .............................................................................. 23
1.5.6 Mechanisms of differential gene expression: pre-mRNA processing ................................................................ 25
1.5.7 Mechanisms of differential gene expression: mRNA translation ...................................................................... 25
1.5.8 Mechanisms of differential gene expression: posttranslational modification ................................................... 26
1.6 THE BASIC TOOLS OF DEVELOPMENTAL GENETICS ................................................................................................................. 26
1.6.1 Characterizing gene expression ....................................................................................................................... 26
1.6.2 Testing gene function ...................................................................................................................................... 27
1.7 PERSONHOOD ............................................................................................................................................................ 27
H2: PREIMPLANTATION DEVELOPMENT ........................................................................................................................... 30
2.1 FERTILIZATION ............................................................................................................................................................ 30
2.1.1 Structure of the gametes ................................................................................................................................ 31
2.1.2 An example: external fertilization in sea urchins .............................................................................................. 33
2.2 EARLY CLEAVAGE ......................................................................................................................................................... 37
2.3 COMPACTION ............................................................................................................................................................. 39
2.3.1 What is compaction? ...................................................................................................................................... 39
2.3.2 The first decision of the rest of your life: trophoblast or ICM? .......................................................................... 39
2.4 CAVITATION ............................................................................................................................................................... 41
2.5 SORTING ................................................................................................................................................................... 41
2.5.1 Sorting process – initiation: what happens to the trophectoderm cells? .......................................................... 41
2.5.2 Sorting process – continuation: what happens to the ICM? ............................................................................. 42
2.5.3 Sorting process – termination: what happens to the ICM? .............................................................................. 42
2.6 HATCHING ................................................................................................................................................................. 43
H3: GASTRULATION .......................................................................................................................................................... 44
3.1 GENERAL INTRODUCTION .............................................................................................................................................. 44
, 3.1.1 Where is gastrulation situated? ...................................................................................................................... 44
3.1.2 Cell movements during gastrulation................................................................................................................ 45
3.1.3 Axis formation ................................................................................................................................................ 45
3.2 FROM THE LATE BLASTOCYST TO LATE EGG CYLINDER............................................................................................................. 46
3.2.1 Events that lead to morphological change to the early egg cylinder ................................................................ 46
3.2.2 Breaking of symmetry – early egg cylinder (E5.5) ............................................................................................ 47
3.2.3 A/P axis formation – mid egg cylinder (E6.0) ................................................................................................... 49
3.2.4 Primitive streak formation – late egg cylinder (E6.5) ....................................................................................... 50
3.3 TWINS ...................................................................................................................................................................... 53
H4: STEM CELLS ................................................................................................................................................................ 54
4.1 THE STEM CELL CONCEPT ............................................................................................................................................... 54
4.1.1 Division and self-renewal ................................................................................................................................ 54
4.1.2 Potency defines a stem cell ............................................................................................................................. 55
4.2 STEM CELL REGULATION ................................................................................................................................................ 56
4.3 PLURIPOTENT CELLS IN THE EMBRYO................................................................................................................................. 56
4.4 ADULT STEM CELL NICHES .............................................................................................................................................. 57
H5: ORGANOGENESIS (HEART AND RELATED STRUCTURES) ............................................................................................ 58
5.1 INTRODUCTION ........................................................................................................................................................... 58
5.2 NEURAL TUBE FORMATION ............................................................................................................................................ 58
5.3 MESODERM FORMATION............................................................................................................................................... 60
5.4 PARAXIAL MESODERM .................................................................................................................................................. 61
5.4.1 Somites ........................................................................................................................................................... 61
5.4.2 Cell-fate and regulation .................................................................................................................................. 61
5.5 LATERAL PLATE MESODERM ............................................................................................................................................ 61
5.5.1 The punchline ................................................................................................................................................. 61
5.5.2 LPM: Heart and Circulatory System ................................................................................................................. 62
5.5.3 Heart development ......................................................................................................................................... 62
5.5.4 Blood vessel formation.................................................................................................................................... 68
5.5.5 Hematopoiesis ................................................................................................................................................ 68
H6: REGENERATION .......................................................................................................................................................... 69
6.1 REGENERATION? ......................................................................................................................................................... 69
6.1.1 The problem of regeneration .......................................................................................................................... 69
6.1.2 Regeneration: a recapitulation of embryonic development? ........................................................................... 70
6.1.3 Regeneration vs woudnd healing? .................................................................................................................. 71
6.1.4 Regeneration; an evolutionary perspective ..................................................................................................... 71
6.2 PLANARIAN REGENERATION ........................................................................................................................................... 71
6.2.1 What are planarians? ..................................................................................................................................... 71
6.2.2 Planarian regeneration: the building blocks .................................................................................................... 73
6.2.3 Planarian regeneration: the instructions ......................................................................................................... 77
6.2.4 Toxicological research in planarians ................................................................................................................ 80
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