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Samenvatting/summary developmental biology (specialization biomedical research)
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Summary of all lectures dev. biology in Course 10 (C. elegans). Including pictures and notes of the lectures.
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DEVELOPMENTAL BIOLOGYDevelopmental biology
Lecture 1 – how can you generate a complete organism from one
single fertilized egg cell?
History of dev. Biology
Preformism = theory that believes sperm cells were cells that could carry the preformed offspring.
Aristotle: the idea of epigenisis
• Epigenisis = theory that an organism develops by differentiation from an unstructured egg.
• His writings shaped western philosophy and natural science for greater than 2 thousand
years.
• Aristotle established method for investigation and reasoning.
• Epigenesis: an organism develops gradually from undifferentiated material.
o William Harvey was the first to show that life came from eggs (i.e. embryos from
yolk).
Theory of recapitulation
• Development of the embryo goes through stages that
represent evolution of ancestors.
• “Ontogeny recapitulates phylogeny” is a catchy phrase to
mean that the development of an organism (ontogeny)
expresses all the intermediate forms of its ancestors
throughout evolution (phylogeny).
• Embryonic development represents the history of the
embryo.
• The begin stages of development are compared to other
animals who are believed to have common ancestors.
• Importance of this theory: organisms have common genetic
developmental plans.
Developmental biology (now)
• Development = organisms arise by a relatively slow process of progressive change.
• Development begins with a single cell – the fertilized egg, or zygote (fully undifferentiated
cell), which divides mitotically to produce all the cells of the body (fully differentiated cells).
• Development does not stop at birth, or even at adulthood.
o Every day we replace > 1 gram of skin cells
o Regeneration of severed parts (starfish)
o Metamorphosis (frogs, butterflies).
• Developmental biology is the discipline that studies embryonic development and other
processes related to organism’s development.
1
, DEVELOPMENTAL BIOLOGY
One cell gives rise to the whole body! Where to begin? Polarisation!
Cellular polarization
How is cell polarization established and regulated?
• Extrinsic regulation
o Regulation that comes from outside, a
signal that comes from outside that
leads to regulation in the cell.
o Cell is in close contact with an external
niche (shown in yellow).
o The stem cell is in close contact with the
stem cell niche.
o This contact maintains the potential to
self-renew.
o By orienting its mitotic spindle perpendicularly to the niche surface, it ensures that
only one daughter cell can maintain contact with the stem cell niche and retain the
ability to self-renew.
• Intrinsic regulation
o Some regulators are inside the cell.
o Regulators of self-renewal are localized
asymmetrically.
o They are inherited by only one of the two
daughter cells.
Cells can be polarized in a cell intrinsic manner (by internal cellular signals)
Neuroblasts (drosophila = fruitfly) are progenitors of neurons. In neuroblast are proteins that are
specifically located at one side of the cell and not on the other (red and blue). You can see the
spindle orientation in an asymmetrically dividing neuroblast.
In C. elegans you can see the different proteins localized on the different sides.
2
, DEVELOPMENTAL BIOLOGY
Cells can be polarized in an extrinsic manner (by external cellular signals)
Human crypts: At the bottom of the crypt there are some cells (green). DII4 is a signal given to the
cells around to become more differentiated. The distance between the signal cells and the other cells
is important in the differentiation of the cell. The signal comes outside the effected cell, this makes it
an external signal.
Some cell can be polarized by both intrinsic and extrinsic signals
How is cell intrinsic polarity regulated?
PAR proteins: an internal cellular signal for polarisation
• Par proteins = partitioning defective genes (seen above in the pictures red and green)
• Homologs throughout the animal kingdom
• Organizing cell asymmetry, co-ordinating polarization of
cytoskeleton
Par polarity is well conserved
• PAR polarity is well conserved in different cell types of many
organisms.
• Cell polarity is required to establish distinct functional
domains.
• Domains have distinct compositions for functions.
3
, DEVELOPMENTAL BIOLOGY
• For example: a epithelial cell in the lumen needs to have 2 different parts, because the side
of the cell in contact with the lumen has (for example) the function to absorb food, while the
other side of the cell is not in contact with the lumen and needs to fulfil another function.
Symmetry breaking in the early C. elegans embryo
All of the PAR proteins are enriched to some degree at
or near the cell cortex, and most of the proteins adopt
asymmetric localization patterns as cell polarization
develops
PAR-3 and PAR-6 become enriched in the anterior
cortex during the one-cell stage, and PAR-1 and PAR-2
become enriched in the posterior cortex. PAR-4 and
PAR-5 remain symmetrically localized through this period, and are both cortical and cytoplasmic.
Symmetry breaking
At the beginning is a fertilized cell; a fused
cell with an sperm cell. The entrance of the
sperm in the egg cell defines the polarity the
cell = symmetry breaking. They call it
symmetry breaking, because the unfertilized
eggs are symmetrical, and polarity is not
determined yet before the sperm fertilizes
the egg.
From the moment the symmetry is breaking,
the cell starts to polarize. In the picture is the
symmetry breaking and stages after that
shown.
PAR proteins cause the polarity
establishment, because of the different localization.
The polarity maintenance is caused by the cytoskeleton.
PAR proteins localize in a mutually exclusive manner:
• PAR-3 and PAR-6 are localized on one side of the cell (the same side).
• PAR-2 and PAR-1 are localized on the other side of the cell.
• See the lighter part of the cells in the picture.
• Par proteins drive their own asymmetric localisation.
• When you have a par-2 mutation, the PAR-2 localization is disturbed, but also the PAR-3
localization is changed. They need each other for the perfect localization and polarity.
4
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