Developmental
biology
,
,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
biology
,
,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
