Molecular and
Developmental
Animal Physiology
,H0: Overview of the course
Learning outcomes – 6 credits
• The students gain profound knowledge and insight in the physiology of reproducing and
developing metazoan organisms.
• Students will analyze and integrate information regarding molecular, cellular, organismal and
environmental mechanisms controlling developmental processes, such as gender
determination, reproductive cycle, gametogenesis and fertilization, early embryogenesis and
pattern formation, cell differentiation, programmed cell death, metamorphosis, regeneration,
ageing, diapause and polyphenisms. Processes will be situated in their evolutionary context.
• In addition, the students acquire insight in different approaches employed in modern
research. They can individually communicate the findings of recent scientific reports on
developmental physiological themes to the other students of the course and can critically
analyze, interpret and discuss these findings in group.
Course content:
1. Introductory concepts: historical overview of mile stones in research
2. Reproductive strategies and mechanisms of gender determination in animals: X-
chromosome inactivation; gender-dependent hormonal differences; role of endocrine and
paracrine factors in gonadogenesis, gonadal steroidogenesis and gametogenesis in an
evolutionary context; control of reproduction cycles in vertebrates and invertebrates;
3. Molecular and cellular control mechanisms during early embryogenesis, Drosophila as a
model. Maternal genes, anterior-posterior and dorso-ventral axis formation, segmentation,
homeotic genes, differentiation of body parts
4. The origin of mesoderm in chordates: the molecular biology of the Nieuwkoop center and the
Spemann organizer. Developmental patterns in vertebrates; left-right axis; formation of limbs
5. Programmed cell death
6. Metamorphosis, regeneration and ageing; hormonal regulation of molting and
metamorphosis in insects: signaling pathways controlling lifespan in different metazoans
7. Stem cells and differentiation
8. Environment and development: diapause; polyphenisms (e.g. phase transition in locusts)
9. Macroevolution and development (molecular evo-devo aspects)
10. Examples and methods illustrating the role of intercellular interaction and communication in
developmental processes, and the regulation of gene expression at the transcriptional,
translational or post-translational level
The exam
The exam will be a written exam: explain a few terms, a few research techniques, and some
open questions.
Final grade:
• Written exam: 15 points
• Presentation: 3 points
• Q&A peers: 2 points
,H1: PRINCIPLES OF DEVELOPMENT ................................................................................................ 1
1.1 A GENERAL INTRODUCTION .................................................................................................................... 1
1.2 HISTORICAL FOUNDATIONS & APPROACHES TO STUDY DEVELOPMENT ............................................................. 6
H2: DIFFERENTIAL GENE EXPRESSION ...........................................................................................26
2.1 GENE EXPRESSION IN DEVELOPMENT ..................................................................................................... 26
2.2 FUNCTIONAL ORGANIZATION AND ANATOMY OF THE GENE (BACKGROUND) .................................................... 29
2.3 MECHANISMS OF DIFFERENTIAL GENE EXPRESSION ................................................................................... 32
2.4 THE BASIC TOOLS OF DEVELOPMENTAL GENETICS ...................................................................................... 37
H3: CELL-TO-CELL COMMUNICATION ............................................................................................43
3.1 CELL COMMUNICATION – FUNDAMENTAL CONCEPTS ................................................................................. 43
3.2 ADHESION AND SORTING: THE PHYSICS OF MORPHOGENESIS ....................................................................... 44
3.3 THE EXTRACELLULAR MATRIX AS SOURCE OF DEVELOPMENTAL SIGNALS ......................................................... 47
3.4 THE EPITHELIAL-MESENCHYMAL TRANSITION (EMT) ................................................................................. 48
3.5 CELL SIGNALING: INDUCTION AND COMPETENCE ...................................................................................... 49
3.6 MORPHOGEN GRADIENTS AND SIGNAL TRANSDUCTION CASCADES ............................................................... 50
3.7 PARACRINE SIGNALING FAMILIES: INDUCERS AND MORPHOGENS.................................................................. 52
3.8 JUXTACRINE SIGNALING FOR CELL IDENTITY .............................................................................................. 60
H4: STEM CELLS ............................................................................................................................61
4.1 THE STEM CELL CONCEPT ..................................................................................................................... 61
4.2 STEM CELL REGULATION ...................................................................................................................... 63
4.3 PLURIPOTENT STEM CELLS IN THE EMBRYO .............................................................................................. 63
4.4 ADULT STEM CELL NICHES .................................................................................................................... 64
H5: EARLY DEVELOPMENT: INVERTEBRATES ..................................................................................65
5.1 CAENORHABDITIS ELEGANS .................................................................................................................. 66
5.2 DROSOPHILA MELANOGASTER .............................................................................................................. 70
H6: EARLY DEVELOPMENT IN VERTEBRATES ..................................................................................84
6.1 AMPHIBIANS – XENOPUS LAEVIS ........................................................................................................... 84
6.2 ZEBRAFISH – DANIO RERIO ................................................................................................................ 100
6.3 BIRDS – AVES ................................................................................................................................. 105
6.4 MAMMALS – MAMMALIA................................................................................................................. 110
6.5 OVERVIEW DEVELOPMENT IN VERTEBRATES ........................................................................................... 116
H7: SEX DETERMINATION ........................................................................................................... 117
7.1 CHROMOSOMAL SEX DETERMINATION IN PLACENTAL MAMMALS................................................................ 118
7.2 CHROMOSOMAL SEX DETERMINATION IN DROSOPHILA ............................................................................ 127
H8: DEVELOPMENT OF THE TETRAPOD LIMB .............................................................................. 130
8.1 GENERAL ANATOMY AND DEVELOPMENT OF THE LIMB ............................................................................. 130
8.2 DETERMINING WHAT KIND OF LIMB TO FORM AND WHERE TO PUT IT .......................................................... 132
8.3 OUTGROWTH: GENERATING THE PROXIMAL-DISTAL AXIS .......................................................................... 134
8.4 SPECIFYING THE ANTERIOR-POSTERIOR AXIS .......................................................................................... 137
, 8.5 GENERATING THE DORSAL-VENTRAL AXIS .............................................................................................. 140
8.6 CELL DEATH AND THE FORMATION OF DIGITS.......................................................................................... 141
H9: METAMORPHOSIS ................................................................................................................ 142
9.1 METAMORPHOSIS IN AMPHIBIANS ....................................................................................................... 142
9.2 METAMORPHOSIS IN INSECTS ............................................................................................................. 145
H10: REGENERATION .................................................................................................................. 148
10.1 REGENERATION? ........................................................................................................................... 148
10.2 HYDRA REGENERATION ................................................................................................................... 151
10.3 PLANARIAN REGENERATION ............................................................................................................. 152
10.4 AMPHIBIAN REGENERATION ............................................................................................................. 160
10.5 ZEBRAFISH REGENERATION .............................................................................................................. 162
10.6 MAMMALIAN REGENERATION .......................................................................................................... 164
Developmental
Animal Physiology
,H0: Overview of the course
Learning outcomes – 6 credits
• The students gain profound knowledge and insight in the physiology of reproducing and
developing metazoan organisms.
• Students will analyze and integrate information regarding molecular, cellular, organismal and
environmental mechanisms controlling developmental processes, such as gender
determination, reproductive cycle, gametogenesis and fertilization, early embryogenesis and
pattern formation, cell differentiation, programmed cell death, metamorphosis, regeneration,
ageing, diapause and polyphenisms. Processes will be situated in their evolutionary context.
• In addition, the students acquire insight in different approaches employed in modern
research. They can individually communicate the findings of recent scientific reports on
developmental physiological themes to the other students of the course and can critically
analyze, interpret and discuss these findings in group.
Course content:
1. Introductory concepts: historical overview of mile stones in research
2. Reproductive strategies and mechanisms of gender determination in animals: X-
chromosome inactivation; gender-dependent hormonal differences; role of endocrine and
paracrine factors in gonadogenesis, gonadal steroidogenesis and gametogenesis in an
evolutionary context; control of reproduction cycles in vertebrates and invertebrates;
3. Molecular and cellular control mechanisms during early embryogenesis, Drosophila as a
model. Maternal genes, anterior-posterior and dorso-ventral axis formation, segmentation,
homeotic genes, differentiation of body parts
4. The origin of mesoderm in chordates: the molecular biology of the Nieuwkoop center and the
Spemann organizer. Developmental patterns in vertebrates; left-right axis; formation of limbs
5. Programmed cell death
6. Metamorphosis, regeneration and ageing; hormonal regulation of molting and
metamorphosis in insects: signaling pathways controlling lifespan in different metazoans
7. Stem cells and differentiation
8. Environment and development: diapause; polyphenisms (e.g. phase transition in locusts)
9. Macroevolution and development (molecular evo-devo aspects)
10. Examples and methods illustrating the role of intercellular interaction and communication in
developmental processes, and the regulation of gene expression at the transcriptional,
translational or post-translational level
The exam
The exam will be a written exam: explain a few terms, a few research techniques, and some
open questions.
Final grade:
• Written exam: 15 points
• Presentation: 3 points
• Q&A peers: 2 points
,H1: PRINCIPLES OF DEVELOPMENT ................................................................................................ 1
1.1 A GENERAL INTRODUCTION .................................................................................................................... 1
1.2 HISTORICAL FOUNDATIONS & APPROACHES TO STUDY DEVELOPMENT ............................................................. 6
H2: DIFFERENTIAL GENE EXPRESSION ...........................................................................................26
2.1 GENE EXPRESSION IN DEVELOPMENT ..................................................................................................... 26
2.2 FUNCTIONAL ORGANIZATION AND ANATOMY OF THE GENE (BACKGROUND) .................................................... 29
2.3 MECHANISMS OF DIFFERENTIAL GENE EXPRESSION ................................................................................... 32
2.4 THE BASIC TOOLS OF DEVELOPMENTAL GENETICS ...................................................................................... 37
H3: CELL-TO-CELL COMMUNICATION ............................................................................................43
3.1 CELL COMMUNICATION – FUNDAMENTAL CONCEPTS ................................................................................. 43
3.2 ADHESION AND SORTING: THE PHYSICS OF MORPHOGENESIS ....................................................................... 44
3.3 THE EXTRACELLULAR MATRIX AS SOURCE OF DEVELOPMENTAL SIGNALS ......................................................... 47
3.4 THE EPITHELIAL-MESENCHYMAL TRANSITION (EMT) ................................................................................. 48
3.5 CELL SIGNALING: INDUCTION AND COMPETENCE ...................................................................................... 49
3.6 MORPHOGEN GRADIENTS AND SIGNAL TRANSDUCTION CASCADES ............................................................... 50
3.7 PARACRINE SIGNALING FAMILIES: INDUCERS AND MORPHOGENS.................................................................. 52
3.8 JUXTACRINE SIGNALING FOR CELL IDENTITY .............................................................................................. 60
H4: STEM CELLS ............................................................................................................................61
4.1 THE STEM CELL CONCEPT ..................................................................................................................... 61
4.2 STEM CELL REGULATION ...................................................................................................................... 63
4.3 PLURIPOTENT STEM CELLS IN THE EMBRYO .............................................................................................. 63
4.4 ADULT STEM CELL NICHES .................................................................................................................... 64
H5: EARLY DEVELOPMENT: INVERTEBRATES ..................................................................................65
5.1 CAENORHABDITIS ELEGANS .................................................................................................................. 66
5.2 DROSOPHILA MELANOGASTER .............................................................................................................. 70
H6: EARLY DEVELOPMENT IN VERTEBRATES ..................................................................................84
6.1 AMPHIBIANS – XENOPUS LAEVIS ........................................................................................................... 84
6.2 ZEBRAFISH – DANIO RERIO ................................................................................................................ 100
6.3 BIRDS – AVES ................................................................................................................................. 105
6.4 MAMMALS – MAMMALIA................................................................................................................. 110
6.5 OVERVIEW DEVELOPMENT IN VERTEBRATES ........................................................................................... 116
H7: SEX DETERMINATION ........................................................................................................... 117
7.1 CHROMOSOMAL SEX DETERMINATION IN PLACENTAL MAMMALS................................................................ 118
7.2 CHROMOSOMAL SEX DETERMINATION IN DROSOPHILA ............................................................................ 127
H8: DEVELOPMENT OF THE TETRAPOD LIMB .............................................................................. 130
8.1 GENERAL ANATOMY AND DEVELOPMENT OF THE LIMB ............................................................................. 130
8.2 DETERMINING WHAT KIND OF LIMB TO FORM AND WHERE TO PUT IT .......................................................... 132
8.3 OUTGROWTH: GENERATING THE PROXIMAL-DISTAL AXIS .......................................................................... 134
8.4 SPECIFYING THE ANTERIOR-POSTERIOR AXIS .......................................................................................... 137
, 8.5 GENERATING THE DORSAL-VENTRAL AXIS .............................................................................................. 140
8.6 CELL DEATH AND THE FORMATION OF DIGITS.......................................................................................... 141
H9: METAMORPHOSIS ................................................................................................................ 142
9.1 METAMORPHOSIS IN AMPHIBIANS ....................................................................................................... 142
9.2 METAMORPHOSIS IN INSECTS ............................................................................................................. 145
H10: REGENERATION .................................................................................................................. 148
10.1 REGENERATION? ........................................................................................................................... 148
10.2 HYDRA REGENERATION ................................................................................................................... 151
10.3 PLANARIAN REGENERATION ............................................................................................................. 152
10.4 AMPHIBIAN REGENERATION ............................................................................................................. 160
10.5 ZEBRAFISH REGENERATION .............................................................................................................. 162
10.6 MAMMALIAN REGENERATION .......................................................................................................... 164
