Medical
Biology
Year 3
Quarter 2
2020
Molecular principles of
Development
SUMMARY OF THE COURSE MOLECULAR PRINCIPLES OF DEVELOPMENT
ELISE REUVEKAMP
EXAM DATE: 07/01/2021
,Inhoud
1: Introduction into the basics of Molecular Developmental Biology .................................................... 3
Overview of development, model system life cycles ...................................................................... 3
Body axes and patterning ................................................................................................................ 4
Germ layers, induction, fate and determination............................................................................. 6
2/3: Axis formation and induction of germ layers in vertebrates I ......................................................... 8
Maternal to zygotic transition ............................................................................................................. 8
Mid-blastula transition ........................................................................................................................ 8
Dorsal-Ventral body axis ..................................................................................................................... 9
Formation DV axis; frogs versus zebrafish: ................................................................................... 11
Gastrulation and fate maps ............................................................................................................... 12
Zebrafish vs Xenopus ..................................................................................................................... 13
Mesoderm induction ......................................................................................................................... 14
Patterning of the germ layers............................................................................................................ 16
Early development and germ layers in mouse: Axis determination ................................................. 17
Early development and germ layers in mouse: Fate map, mesoderm induction and patterning .... 18
4: Morphogenesis .................................................................................................................................. 20
Principles of cell adhesion ................................................................................................................. 20
Cadherins ....................................................................................................................................... 21
Immunoglobulin superfamily ........................................................................................................ 21
Integrins ......................................................................................................................................... 21
Gastrulation movements (in Xenopus) ............................................................................................. 22
Involution ...................................................................................................................................... 23
Convergent extension ................................................................................................................... 23
Epiboly ........................................................................................................................................... 24
5: AP patterning and Hox gene function ............................................................................................... 25
The origin of somites ......................................................................................................................... 25
Signalling pathways involved in somite formation ........................................................................... 26
The temporal order of somite formation .......................................................................................... 26
The clock and wavefront model of somite formation ....................................................................... 27
Hox gene ........................................................................................................................................... 28
temporal and spatial expression of hox genes .................................................................................. 28
Function of several members of hox genes ...................................................................................... 29
Posterior dominance model of hox gene expression ........................................................................ 30
Molecular control of Hox gene expression ....................................................................................... 31
6: Organogenesis ................................................................................................................................... 32
, Important structures: limb bud, AER, ZPA and ectoderm ................................................................. 32
Patterning along three axis ............................................................................................................... 33
Overview axes patterning and their effects on one another ........................................................ 35
Self-organization of the limb bud ...................................................................................................... 35
Origin of limb muscle cells................................................................................................................. 36
Separation of digits ........................................................................................................................... 36
Gene regulation in limb development and disease .......................................................................... 36
7: Germ cell development ..................................................................................................................... 40
Germ cell specification and migration .............................................................................................. 40
Meiosis .............................................................................................................................................. 42
Genomic imprinting ........................................................................................................................... 44
8: Fertilization and determination of sexual phenotype....................................................................... 47
Fertilization........................................................................................................................................ 47
Changes in the egg plasma membrane and enveloping layers at fertilization block polyspermy 48
Sex determination ............................................................................................................................. 50
Dosage compensation ....................................................................................................................... 51
X chromosome inactivation............................................................................................................... 51
9/10: Cell differentiation ....................................................................................................................... 52
Transcription regulation in cell differentiation ................................................................................. 52
Stem cells and their niche ................................................................................................................. 53
Cellular reprogramming .................................................................................................................... 55
Stem cells in homeostasis and repair and regenerative medicine.................................................... 55
11: Evo Devo .......................................................................................................................................... 55
Questions: ............................................................................................................................................. 56
, Molecular principles of development
1: Introduction into the basics of Molecular Developmental Biology
Forward genetics is when a mutation in a gene of interest is induced and analyse the phenotype.
Some phenotypes may be lethal but others can be interesting. Then it is identified what genes cause
the interesting phenotypes. (so, from phenotype → gene)
Opposite to reverse genetics where you want to know the function of a gene
Drosophila serve as an example (→ box 2A). There are four Drosophila chromosomes, which all get a
separate screen. The chromosome of interest in oocytes has temperature-sensitive mutation and by
elimination of individuals with two wt alleles. The sperm mutation is random by irradiation, but the
chromosome of interest carries a visual marker in the progeny.
The forward genetics can be used to identify the major players in a genetic model system. A whole
series of genes involved in patterning named; gap genes, pair rule genes and segment polarity genes
were found using forward genetics. Those three categories of genes, allow the embryo to become
segmented.
Homeotic genes, which regulate the development of anatomical structures determine the identity of
body segments. The organization of the hox genes in the chromosome is similar to the order of their
expression along the AP axis of the developing animal, and are thus said to display collinearity. Hox
genes were found to be involved in patterning.
Overview of development, model system life cycles
The life cycle of Drosophila melanogaster:
It takes only 9 days to develop an adult fly from a fertilized
egg.
The sperm enters through the micropyle. The cell is
elongated and has polarity, as it has two sides. One end
with the micropyle and the other end where the germline
is and gametes are formed (pole cells)
A syncytium is formed in early development, it
is a big bag of cytoplasm containing multiple
nuclei. This is because the nuclei have divided
but the cells did not. So there is nuclear
division without cytokinesis.
The nuclei migrate to the periphery of the
cytoplasm and form membranes around them
to form a cellular blastoderm from the
syncytial blastoderm.
The syncytium allows for diffusion of molecules, which has important consequences for
developmental mechanisms which act in the drosophila embryo.
Biology
Year 3
Quarter 2
2020
Molecular principles of
Development
SUMMARY OF THE COURSE MOLECULAR PRINCIPLES OF DEVELOPMENT
ELISE REUVEKAMP
EXAM DATE: 07/01/2021
,Inhoud
1: Introduction into the basics of Molecular Developmental Biology .................................................... 3
Overview of development, model system life cycles ...................................................................... 3
Body axes and patterning ................................................................................................................ 4
Germ layers, induction, fate and determination............................................................................. 6
2/3: Axis formation and induction of germ layers in vertebrates I ......................................................... 8
Maternal to zygotic transition ............................................................................................................. 8
Mid-blastula transition ........................................................................................................................ 8
Dorsal-Ventral body axis ..................................................................................................................... 9
Formation DV axis; frogs versus zebrafish: ................................................................................... 11
Gastrulation and fate maps ............................................................................................................... 12
Zebrafish vs Xenopus ..................................................................................................................... 13
Mesoderm induction ......................................................................................................................... 14
Patterning of the germ layers............................................................................................................ 16
Early development and germ layers in mouse: Axis determination ................................................. 17
Early development and germ layers in mouse: Fate map, mesoderm induction and patterning .... 18
4: Morphogenesis .................................................................................................................................. 20
Principles of cell adhesion ................................................................................................................. 20
Cadherins ....................................................................................................................................... 21
Immunoglobulin superfamily ........................................................................................................ 21
Integrins ......................................................................................................................................... 21
Gastrulation movements (in Xenopus) ............................................................................................. 22
Involution ...................................................................................................................................... 23
Convergent extension ................................................................................................................... 23
Epiboly ........................................................................................................................................... 24
5: AP patterning and Hox gene function ............................................................................................... 25
The origin of somites ......................................................................................................................... 25
Signalling pathways involved in somite formation ........................................................................... 26
The temporal order of somite formation .......................................................................................... 26
The clock and wavefront model of somite formation ....................................................................... 27
Hox gene ........................................................................................................................................... 28
temporal and spatial expression of hox genes .................................................................................. 28
Function of several members of hox genes ...................................................................................... 29
Posterior dominance model of hox gene expression ........................................................................ 30
Molecular control of Hox gene expression ....................................................................................... 31
6: Organogenesis ................................................................................................................................... 32
, Important structures: limb bud, AER, ZPA and ectoderm ................................................................. 32
Patterning along three axis ............................................................................................................... 33
Overview axes patterning and their effects on one another ........................................................ 35
Self-organization of the limb bud ...................................................................................................... 35
Origin of limb muscle cells................................................................................................................. 36
Separation of digits ........................................................................................................................... 36
Gene regulation in limb development and disease .......................................................................... 36
7: Germ cell development ..................................................................................................................... 40
Germ cell specification and migration .............................................................................................. 40
Meiosis .............................................................................................................................................. 42
Genomic imprinting ........................................................................................................................... 44
8: Fertilization and determination of sexual phenotype....................................................................... 47
Fertilization........................................................................................................................................ 47
Changes in the egg plasma membrane and enveloping layers at fertilization block polyspermy 48
Sex determination ............................................................................................................................. 50
Dosage compensation ....................................................................................................................... 51
X chromosome inactivation............................................................................................................... 51
9/10: Cell differentiation ....................................................................................................................... 52
Transcription regulation in cell differentiation ................................................................................. 52
Stem cells and their niche ................................................................................................................. 53
Cellular reprogramming .................................................................................................................... 55
Stem cells in homeostasis and repair and regenerative medicine.................................................... 55
11: Evo Devo .......................................................................................................................................... 55
Questions: ............................................................................................................................................. 56
, Molecular principles of development
1: Introduction into the basics of Molecular Developmental Biology
Forward genetics is when a mutation in a gene of interest is induced and analyse the phenotype.
Some phenotypes may be lethal but others can be interesting. Then it is identified what genes cause
the interesting phenotypes. (so, from phenotype → gene)
Opposite to reverse genetics where you want to know the function of a gene
Drosophila serve as an example (→ box 2A). There are four Drosophila chromosomes, which all get a
separate screen. The chromosome of interest in oocytes has temperature-sensitive mutation and by
elimination of individuals with two wt alleles. The sperm mutation is random by irradiation, but the
chromosome of interest carries a visual marker in the progeny.
The forward genetics can be used to identify the major players in a genetic model system. A whole
series of genes involved in patterning named; gap genes, pair rule genes and segment polarity genes
were found using forward genetics. Those three categories of genes, allow the embryo to become
segmented.
Homeotic genes, which regulate the development of anatomical structures determine the identity of
body segments. The organization of the hox genes in the chromosome is similar to the order of their
expression along the AP axis of the developing animal, and are thus said to display collinearity. Hox
genes were found to be involved in patterning.
Overview of development, model system life cycles
The life cycle of Drosophila melanogaster:
It takes only 9 days to develop an adult fly from a fertilized
egg.
The sperm enters through the micropyle. The cell is
elongated and has polarity, as it has two sides. One end
with the micropyle and the other end where the germline
is and gametes are formed (pole cells)
A syncytium is formed in early development, it
is a big bag of cytoplasm containing multiple
nuclei. This is because the nuclei have divided
but the cells did not. So there is nuclear
division without cytokinesis.
The nuclei migrate to the periphery of the
cytoplasm and form membranes around them
to form a cellular blastoderm from the
syncytial blastoderm.
The syncytium allows for diffusion of molecules, which has important consequences for
developmental mechanisms which act in the drosophila embryo.
