Developmental biology
Inhoud
Chapter 1: Fate and Potency ................................................................................................................................... 4
Cell division.......................................................................................................................................................... 4
Differentiation ..................................................................................................................................................... 5
Growth................................................................................................................................................................. 6
Migration ............................................................................................................................................................. 6
Patterning ............................................................................................................................................................ 7
Morphogenesis.................................................................................................................................................... 7
Apoptosis ............................................................................................................................................................. 7
Early development in mammals........................................................................................................................... 7
Chapter 2: Model organisms ................................................................................................................................. 11
Hydra ................................................................................................................................................................. 11
C. elegans (worm) .............................................................................................................................................. 11
Fruit fly .............................................................................................................................................................. 11
Frog (Xenopus) .................................................................................................................................................. 11
Zebrafish ............................................................................................................................................................ 12
Chicken .............................................................................................................................................................. 12
Mouse ............................................................................................................................................................... 12
Chapter 3: Methods in developmental biology..................................................................................................... 13
Manipulating embryo’s ..................................................................................................................................... 13
Molecules and embryo’s .................................................................................................................................... 14
Genes, gene networks and embryos................................................................................................................... 14
Deciphering gene function ................................................................................................................................. 16
Development and evolution .............................................................................................................................. 16
Chapter 4: Signaling pathways ..................................................................................................................................... 17
Ligands ............................................................................................................................................................... 17
Receptors........................................................................................................................................................... 18
Intracellular players ........................................................................................................................................... 22
Conclusion ........................................................................................................................................................ 23
Chapter 5: Gastrulation .............................................................................................................................................. 24
Gastrulation in the frog ...................................................................................................................................... 25
Gastrulation in zebrafish .................................................................................................................................... 29
Gastrulation in the chicken ................................................................................................................................. 31
Gastrulation in the mouse ................................................................................................................................. 31
Gastrulation in human....................................................................................................................................... 33
Modeling gastrulation ....................................................................................................................................... 33
1
, Physiological and pathological EMT .................................................................................................................. 34
Conclusion ........................................................................................................................................................ 34
Chapter 6: Positional information ................................................................................................................................ 35
The French flag model ....................................................................................................................................... 36
Positional information in Drosophila ................................................................................................................ 36
Conclusion ......................................................................................................................................................... 39
Chapter 7: Mesoderm and neuroectoderm patterning .................................................................................................. 40
Mesoderm patterning in the frog ..................................................................................................................... 40
Mesoderm patterning in mouse ....................................................................................................................... 42
Ectoderm development..................................................................................................................................... 42
Neural crest cells ............................................................................................................................................... 46
Neural crest syndromes ..................................................................................................................................... 47
Chapter 8: Somitogenesis and limb development ........................................................................................................ 48
Differentiation of somites ................................................................................................................................. 48
Limb development ............................................................................................................................................ 49
Digits .................................................................................................................................................................. 53
Chapter 9: Anterior-Posterior patterning ............................................................................................................. 54
Lewis model....................................................................................................................................................... 54
Homeobox encodes the homeodomain............................................................................................................ 55
Chapter 10: Folding morphogenesis ............................................................................................................................. 56
From trilaminar to tube-in-a-tube embryo ....................................................................................................... 56
Ventrolateral folding morphogenesis ............................................................................................................... 56
Ventro-lateral morphogenesis in human .......................................................................................................... 59
Human disorders ............................................................................................................................................... 61
Chapter 11: Branching morphogenesis ......................................................................................................................... 62
Branched structures .......................................................................................................................................... 62
Branching morphogenesis ................................................................................................................................. 62
Vasculature development ................................................................................................................................. 63
Tracheal system................................................................................................................................................. 64
Lung development............................................................................................................................................. 65
Kidney development ......................................................................................................................................... 65
Mammary gland ................................................................................................................................................ 66
Common mechanisms ....................................................................................................................................... 67
Congenital disorders ......................................................................................................................................... 67
Chapter 12: Eye development ..................................................................................................................................... 68
Adult mammalian eye ....................................................................................................................................... 68
Adult Drosophila eye ......................................................................................................................................... 69
Eye development in mammals .......................................................................................................................... 69
Eye development in Drosophila ........................................................................................................................ 70
2
, Inspirational experiments ................................................................................................................................. 70
Deciphering molecular mechanisms ................................................................................................................. 71
Implications in biomedicine .............................................................................................................................. 73
Chapter 13: Development in a dish............................................................................................................................... 74
Embryonic stem cells (ESC) ............................................................................................................................... 74
Adult stem cells ................................................................................................................................................. 74
What can we do with stem cells? ...................................................................................................................... 75
Induced pluripotent stem cells (iPSC) ............................................................................................................... 75
Organoids .......................................................................................................................................................... 76
Chapter 14: Birth defects and teratogens ............................................................................................................. 77
Birth defects ...................................................................................................................................................... 77
Teratology ......................................................................................................................................................... 78
When is exposure to a toxic agent the cause of a birth defect? ....................................................................... 79
3
, Chapter 1: Fate and Potency
Fate = Describes what a cell will normally develop into. However, having a particular fate does not imply that
the cell could not develop differently if placed in a different environment.
Fate map = Map or diagram based on having followed cell lineage from specific regions of the embryo to
“map” larval or adult structures into the region of the embryo from which they arose (= lineage tracing). To
study the embryonic origin of various adult tissues and structures. The "fate" of each cell or group of cells is
mapped onto the embryo, showing which parts of the embryo will develop into which tissue.
1. Cell division
2. Differentiation
3. Growth
4. Migration
5. Patterning
6. Morphogenesis
7. Apoptosis
Zygote → blastula/blastocyst → gastrula → neurula
Cell division
Embryonic cleavage vs. somatic cell divisions
→ somatic cell cycle: G1-S-G2-M (slow: for animals inside uterus)
→ cleavage cycle: S-M (very fast: necessary for animals outside uterus)
Symmetric divisions = the daughter cells have the same fate
Asymmetric divisions = the daughter cells have different fates
Maternal mRNA are laid down in the oocyte during oogenesis, after fertilization new proteins are synthesized
from maternal mRNA. Transcription from embryo’s own genes (zygotic genome) starts 2-16 cells stage
Blastomeres = cells of the zygote that will undergo cleavage (controlled by maternal factors). So this is the first
thing that happens after fertilization.
Embryonic cleavage = The embryo divides into smaller and smaller cells without the cytoplasmic volume being
increased. (no gap phases: no cell growth or protein expression)
Patterns of embryonic cleavage
The amount and distribution of the yolk determines at which side (so where) cleavage will occur and also the
relative size of the blastomeres.
Factors in the cytoplasm influence the angle of the mitotic spindle and timing of its formation.
Holoblastic cleavage involves the division of the entire egg into blastomeres.
→ patterns followed by these cells during cleavage are radial, spiral, rotational, and bilateral.
Meroblastic cleavage involves early separation between cells at the animal pole and yolk at the vegetal pole.
Synctium = a single cell or cytoplasmic mass containing several nuclei: fusion of cells or by division of nuclei
4
Inhoud
Chapter 1: Fate and Potency ................................................................................................................................... 4
Cell division.......................................................................................................................................................... 4
Differentiation ..................................................................................................................................................... 5
Growth................................................................................................................................................................. 6
Migration ............................................................................................................................................................. 6
Patterning ............................................................................................................................................................ 7
Morphogenesis.................................................................................................................................................... 7
Apoptosis ............................................................................................................................................................. 7
Early development in mammals........................................................................................................................... 7
Chapter 2: Model organisms ................................................................................................................................. 11
Hydra ................................................................................................................................................................. 11
C. elegans (worm) .............................................................................................................................................. 11
Fruit fly .............................................................................................................................................................. 11
Frog (Xenopus) .................................................................................................................................................. 11
Zebrafish ............................................................................................................................................................ 12
Chicken .............................................................................................................................................................. 12
Mouse ............................................................................................................................................................... 12
Chapter 3: Methods in developmental biology..................................................................................................... 13
Manipulating embryo’s ..................................................................................................................................... 13
Molecules and embryo’s .................................................................................................................................... 14
Genes, gene networks and embryos................................................................................................................... 14
Deciphering gene function ................................................................................................................................. 16
Development and evolution .............................................................................................................................. 16
Chapter 4: Signaling pathways ..................................................................................................................................... 17
Ligands ............................................................................................................................................................... 17
Receptors........................................................................................................................................................... 18
Intracellular players ........................................................................................................................................... 22
Conclusion ........................................................................................................................................................ 23
Chapter 5: Gastrulation .............................................................................................................................................. 24
Gastrulation in the frog ...................................................................................................................................... 25
Gastrulation in zebrafish .................................................................................................................................... 29
Gastrulation in the chicken ................................................................................................................................. 31
Gastrulation in the mouse ................................................................................................................................. 31
Gastrulation in human....................................................................................................................................... 33
Modeling gastrulation ....................................................................................................................................... 33
1
, Physiological and pathological EMT .................................................................................................................. 34
Conclusion ........................................................................................................................................................ 34
Chapter 6: Positional information ................................................................................................................................ 35
The French flag model ....................................................................................................................................... 36
Positional information in Drosophila ................................................................................................................ 36
Conclusion ......................................................................................................................................................... 39
Chapter 7: Mesoderm and neuroectoderm patterning .................................................................................................. 40
Mesoderm patterning in the frog ..................................................................................................................... 40
Mesoderm patterning in mouse ....................................................................................................................... 42
Ectoderm development..................................................................................................................................... 42
Neural crest cells ............................................................................................................................................... 46
Neural crest syndromes ..................................................................................................................................... 47
Chapter 8: Somitogenesis and limb development ........................................................................................................ 48
Differentiation of somites ................................................................................................................................. 48
Limb development ............................................................................................................................................ 49
Digits .................................................................................................................................................................. 53
Chapter 9: Anterior-Posterior patterning ............................................................................................................. 54
Lewis model....................................................................................................................................................... 54
Homeobox encodes the homeodomain............................................................................................................ 55
Chapter 10: Folding morphogenesis ............................................................................................................................. 56
From trilaminar to tube-in-a-tube embryo ....................................................................................................... 56
Ventrolateral folding morphogenesis ............................................................................................................... 56
Ventro-lateral morphogenesis in human .......................................................................................................... 59
Human disorders ............................................................................................................................................... 61
Chapter 11: Branching morphogenesis ......................................................................................................................... 62
Branched structures .......................................................................................................................................... 62
Branching morphogenesis ................................................................................................................................. 62
Vasculature development ................................................................................................................................. 63
Tracheal system................................................................................................................................................. 64
Lung development............................................................................................................................................. 65
Kidney development ......................................................................................................................................... 65
Mammary gland ................................................................................................................................................ 66
Common mechanisms ....................................................................................................................................... 67
Congenital disorders ......................................................................................................................................... 67
Chapter 12: Eye development ..................................................................................................................................... 68
Adult mammalian eye ....................................................................................................................................... 68
Adult Drosophila eye ......................................................................................................................................... 69
Eye development in mammals .......................................................................................................................... 69
Eye development in Drosophila ........................................................................................................................ 70
2
, Inspirational experiments ................................................................................................................................. 70
Deciphering molecular mechanisms ................................................................................................................. 71
Implications in biomedicine .............................................................................................................................. 73
Chapter 13: Development in a dish............................................................................................................................... 74
Embryonic stem cells (ESC) ............................................................................................................................... 74
Adult stem cells ................................................................................................................................................. 74
What can we do with stem cells? ...................................................................................................................... 75
Induced pluripotent stem cells (iPSC) ............................................................................................................... 75
Organoids .......................................................................................................................................................... 76
Chapter 14: Birth defects and teratogens ............................................................................................................. 77
Birth defects ...................................................................................................................................................... 77
Teratology ......................................................................................................................................................... 78
When is exposure to a toxic agent the cause of a birth defect? ....................................................................... 79
3
, Chapter 1: Fate and Potency
Fate = Describes what a cell will normally develop into. However, having a particular fate does not imply that
the cell could not develop differently if placed in a different environment.
Fate map = Map or diagram based on having followed cell lineage from specific regions of the embryo to
“map” larval or adult structures into the region of the embryo from which they arose (= lineage tracing). To
study the embryonic origin of various adult tissues and structures. The "fate" of each cell or group of cells is
mapped onto the embryo, showing which parts of the embryo will develop into which tissue.
1. Cell division
2. Differentiation
3. Growth
4. Migration
5. Patterning
6. Morphogenesis
7. Apoptosis
Zygote → blastula/blastocyst → gastrula → neurula
Cell division
Embryonic cleavage vs. somatic cell divisions
→ somatic cell cycle: G1-S-G2-M (slow: for animals inside uterus)
→ cleavage cycle: S-M (very fast: necessary for animals outside uterus)
Symmetric divisions = the daughter cells have the same fate
Asymmetric divisions = the daughter cells have different fates
Maternal mRNA are laid down in the oocyte during oogenesis, after fertilization new proteins are synthesized
from maternal mRNA. Transcription from embryo’s own genes (zygotic genome) starts 2-16 cells stage
Blastomeres = cells of the zygote that will undergo cleavage (controlled by maternal factors). So this is the first
thing that happens after fertilization.
Embryonic cleavage = The embryo divides into smaller and smaller cells without the cytoplasmic volume being
increased. (no gap phases: no cell growth or protein expression)
Patterns of embryonic cleavage
The amount and distribution of the yolk determines at which side (so where) cleavage will occur and also the
relative size of the blastomeres.
Factors in the cytoplasm influence the angle of the mitotic spindle and timing of its formation.
Holoblastic cleavage involves the division of the entire egg into blastomeres.
→ patterns followed by these cells during cleavage are radial, spiral, rotational, and bilateral.
Meroblastic cleavage involves early separation between cells at the animal pole and yolk at the vegetal pole.
Synctium = a single cell or cytoplasmic mass containing several nuclei: fusion of cells or by division of nuclei
4
