Molecular principles of development – Denise Tax
Lecture 1 – Basic concepts
Why developmental biology?
- Fascinating process in body
- Foundational in understanding of life
- Relations between disease, development and differentiation
- Potential of regenerative medicine
Forward genetics: random mutagenesis, screen for phenotypes of interest (different from reverse
genetics: make mutation in gene of interest, then analyse phenotype)
Expression along A-P axis relates to:
- Genomic position
- Timing of expression
Homeotic transformations: switched identity
Life cycle of Drosophila melanogaster:
Syncytium: many nuclei with shared cytoplasm (no cell membranes), this allows for free diffusion of
proteins
,Blastula → Gastrula → Neurula
Gastrulation: is defined as an early developmental process in which an embryo transforms from a
one-dimensional layer of epithelial cells (blastula) and reorganizes into a multi-layered and
multidimensional structure called the gastrula. Gastrulation is the most important step.
Maternal axes and symmetry:
- Drosophila: Anterior-Posterior (A-P), Dorsal-Ventral (D-V)
- Zebrafish, Xenopus: Animal-Vegetal (radial symmetry)
- Mammals: no polarity (point-symmetry)
Syncytium and cleavages:
- Drosophila: Nuclear divisions, syncytium
- Zebrafish: Meroblastic divisions, yolk syncytial layer
- Xenopus, mouse: Holoblastic divisions
Meroblastic division: division is not that the cells
split in two, but on top of the cell the division is
happening.
Holoblastic division: just divides by two the whole
time.
Embryonic patterning is the process of establishing positional information at the molecular level
among similar cells.
Establishes body axes :
Starts with polarity / symmetry-breaking: asymmetric cell divisions, molecular gradients
,Germ layers
Fate maps tell what the progeny of cells will be.
Fate ≠ Specified ≠ Determined
Fate: predicted outcome based on position in embryo, lineage tracing
Specified: signals received that steer lineage decisions, but still reversible
Determined: cells have become irreversibly committed
Detection of protein: immune histochemistry (with antibodies)
Detection of RNA: in situ hybridization (with RNA probes)
Lecture 2 – Axes_Germ layers 1
Cleavage is a type of embryonic cell division: increasing number of cells without increase of total
cytoplasmic volume, so cells become smaller and smaller.
Maternal to zygotic transition (MTZ)
- Maternal RNA degradation
- Zygotic genome activation (ZGA, new embryonic transcription)
Happens at mid-blastula stage in xenopus/zebrafish
Mid-blastula transition (MBT)
- ZGA
- Loss of cell cycle synchrony
- Cells become more motile (cells move around)
- Nucleus-to-cytoplasm ratio changes during early development
Overexpression of replication factors causes additional rapid cell divisions and delay in transcription.
Germ layers and body axes:
- Xenopus
- Maternally derived: ectoderm, endoderm and A-V axis
- Specified post-ZGA: mesoderm, D-V and A-P pattern
, Animal-vegetal polarity in fish and amphibia: radial symmetry of the oocyte (=female gametocyte
or germ cell)
- Animal pole: pigmented (frogs),
pluripotency
- Vegetal pole: yolk (heavy)
Specific mRNAs are transported to the vegetal pole before fertilization.
gdf1 mRNA (Vg-1, TGFβ family)
Breaking radial symmetry by fertilization in Xenopus:
Lecture 1 – Basic concepts
Why developmental biology?
- Fascinating process in body
- Foundational in understanding of life
- Relations between disease, development and differentiation
- Potential of regenerative medicine
Forward genetics: random mutagenesis, screen for phenotypes of interest (different from reverse
genetics: make mutation in gene of interest, then analyse phenotype)
Expression along A-P axis relates to:
- Genomic position
- Timing of expression
Homeotic transformations: switched identity
Life cycle of Drosophila melanogaster:
Syncytium: many nuclei with shared cytoplasm (no cell membranes), this allows for free diffusion of
proteins
,Blastula → Gastrula → Neurula
Gastrulation: is defined as an early developmental process in which an embryo transforms from a
one-dimensional layer of epithelial cells (blastula) and reorganizes into a multi-layered and
multidimensional structure called the gastrula. Gastrulation is the most important step.
Maternal axes and symmetry:
- Drosophila: Anterior-Posterior (A-P), Dorsal-Ventral (D-V)
- Zebrafish, Xenopus: Animal-Vegetal (radial symmetry)
- Mammals: no polarity (point-symmetry)
Syncytium and cleavages:
- Drosophila: Nuclear divisions, syncytium
- Zebrafish: Meroblastic divisions, yolk syncytial layer
- Xenopus, mouse: Holoblastic divisions
Meroblastic division: division is not that the cells
split in two, but on top of the cell the division is
happening.
Holoblastic division: just divides by two the whole
time.
Embryonic patterning is the process of establishing positional information at the molecular level
among similar cells.
Establishes body axes :
Starts with polarity / symmetry-breaking: asymmetric cell divisions, molecular gradients
,Germ layers
Fate maps tell what the progeny of cells will be.
Fate ≠ Specified ≠ Determined
Fate: predicted outcome based on position in embryo, lineage tracing
Specified: signals received that steer lineage decisions, but still reversible
Determined: cells have become irreversibly committed
Detection of protein: immune histochemistry (with antibodies)
Detection of RNA: in situ hybridization (with RNA probes)
Lecture 2 – Axes_Germ layers 1
Cleavage is a type of embryonic cell division: increasing number of cells without increase of total
cytoplasmic volume, so cells become smaller and smaller.
Maternal to zygotic transition (MTZ)
- Maternal RNA degradation
- Zygotic genome activation (ZGA, new embryonic transcription)
Happens at mid-blastula stage in xenopus/zebrafish
Mid-blastula transition (MBT)
- ZGA
- Loss of cell cycle synchrony
- Cells become more motile (cells move around)
- Nucleus-to-cytoplasm ratio changes during early development
Overexpression of replication factors causes additional rapid cell divisions and delay in transcription.
Germ layers and body axes:
- Xenopus
- Maternally derived: ectoderm, endoderm and A-V axis
- Specified post-ZGA: mesoderm, D-V and A-P pattern
, Animal-vegetal polarity in fish and amphibia: radial symmetry of the oocyte (=female gametocyte
or germ cell)
- Animal pole: pigmented (frogs),
pluripotency
- Vegetal pole: yolk (heavy)
Specific mRNAs are transported to the vegetal pole before fertilization.
gdf1 mRNA (Vg-1, TGFβ family)
Breaking radial symmetry by fertilization in Xenopus:
