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Samenvatting MOB-20803 Mechanisms of development (MOB-20803)
Een engelse samenvatting van het vak Mechanisms of development, bevat geen samenvatting van de tutorials, wel van de colleges, opdrachten en computer cases
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Deze samenvatting bevat niet uitgebreide samenvatting van de computer cases en tutorials.De gehele samenvatting is in het Engels. Onderstreept zijn de learning goals zoals
aangegeven in de manual van 2020.
Mechanisms of Development MOB-20803
Learning goals course:
• understand molecular mechanisms that control pattern formation and maintenance of
pluripotency in stem cells
• explain the underlying principles of the regulation of development;
• indicate the similarities and differences between the developmental processes in plants and
animals
Lecture 1 Biological logic and principles of animal development
How did multicellularity originate? It has evolved at least two times, once for plants once for
animals.. also in fungi. But they used the same initial tool kit: the set of genes inherited from their
common unicellular eukaryotic ancestor.
Molecular toolkit available for multicellular development:
all cells
• store their hereditary information in the same linear chemical code (DNA)
• transcribe portions of their hereditary information into the same intermediary form (RNA)
• translate RNA code into protein code
• use proteins as catalysts
• control the activity of individual genes by regulatory proteins binding to DNA (‘transcription
factors’)
all eukaryotes
• have a cytoskeleton (for growth)
• have internal membranes (including a nuclear envelope)
• have mitochondria
So to conclude the genome determines the pattern of development and corrects for the
development in time and space. Developmental biology wants to research how the genome the
pattern determines.
,Genomic equivalence: the genome is identical in each cell, but cells can still be different because of
the different expression of (sets of) genes. Differential gene expression is that not all genes are
expressed in every cell.
Four processes contribute to the mechanisms of development:
• Cell proliferation: producing multiple cells from one cell
• Cell specialization: producing cells with different characteristics at different places at the
right time
• Cell interactions: coordinating the behavior of one cell with that of its neighbors
• Cell movement (only in animals): rearranging cells to make structured organs and tissues
These process occur at the same time and change gene activity, developmental biology wants to
know how these are executed at the right place and time.
Important definitions in developmental biology;
Pattern formation: the process that leads to a spatial pattern of cell specification.
Cell specification: differences in regulators that initiate cell specialization.
Cell differentiation: changes in protein content complete and complete cell specialization.
The key issue in developmental biology is that in architecture we assume that a blueprint and
building blocks lead to a beautiful structure, but in biology the blueprint and building blocks are
entangled.
The central dogma in biology states that DNA is transcribed into RNA that is translated into proteins.
But here the proteins that are transcription factors/regulators, which determine what parts of DNA
are used or not.
Basic machinery of development is in many organism the same
• Evolutionary related molecules have the same functions:
o Define the differences between body regions
o Create body pattern
o Define specialized cell types
• Homologous proteins are often functionally interchangeable between different species
overall logic of development: plants and animals have independently found similar solutions to the
fundamental problems in development
Lecture 2 Principles of plant development and their comparison to animal development
,Why do we want to compare two kingdoms of life? To compare the similar processes to understand
fundamental principles of life since they developed independently (and life originates from one
origin/ancestor)
Formation of a developmental axis: creating different cells along a particular dimension
Animals: anterior- posterior axis (front-backside), dorsoventral axis (belly-back), L/R axis
Plants: apical-basal axis (top-bottom), radial axis (inside-outside), bilateral axis (2sides)
Body architecture during animal embryogenesis: embryos are already developed (body plan ready)
Body architecture during plant embryogenesis: shoot apical meristem and root meristem diversify
body pattern, embryo still needs a lot of development
Plant cells don’t move relative to each other. Tissues form by precisely oriented cell divisions, but
moved cells know their new position by continuous positional information
Main similarities in development in plants and animals: pattern formation by gene regulation
programs (transcription factors), differences in gene expression ( transcription and translation) lead
to different cell types.
Developmental Biology and Evolution:
Development differs between species, this is due to selected mutations.
Proteins are only partially flexible for evolutionary change, transcription factors therefore evolve
slowly.
Many mutations that rapidly change development occur on DNA in TF binding sites, thus influencing
only one target gene.
Auxin and apical-basal axis formation in Arabidopsis
During the first cell cycles auxin maxima are formed at root and embryonic leaf (cotyledon) poles
Auxin-induced transcription factors form gradients
Zygotic PLETHORA gene transcription triggered by auxin maximum in root
Locally produced RNA ->translation of PLT protein ->Divided over daughter cells ->Protein gradient
controls through its many target genes where cells divide and do not differentiate
Plants meristem cells perceive many environmental cues(light, nutrient conditions (and must often
react by developmental processes) Auxin is a long-range plant developmental signal, allows
coordination of development. (auxin and PIN transport protein lead to polar flow)
Arabidopsis thaliana is a model organism because:
• Small plant
• Small genome
• Quick to reproduce
• Convenient for genetics (only 26,000 genes), diploid
• Easy to transform
• Simple growth conditions
• Advantage (like C. Elegans) making it a better model than Drosophila: it can reproduce as a
hermaphrodite (self-fertilize), which makes genetic screens easier
Similar gene regulatory proteins (TFs) occur in plants and animals but their function in development
may be different.
, Plant organs primarily develop post-embryonically by apical meristems.
Long range signal molecules in plants make sure there is coordination in development between
different plant parts that are affected by different environmental cues.
Plants have evolved small molecules as hormones instead of peptides, because these are small
enough to penetrate cell walls.
Animals Plants
Eat other organisms create energy form sunlight
Body plant is ready in embryo embryo and post-embryonic development
No rigid cell wall rigid cell wall, no cell movement
Development is determinate development of organs/units is determinate,
but overall development is not
Development not affected by environment overall development highly controlled by env
No role for long distance signalling long distance signalling of hormones plays
an important role in overall architecture
Endosymbiosis plays minor role endosymbiosis is used for major functions
Pin proteins transport auxin in a polar manner, creating local maxima of auxin/polarized auxin
transport controls the pattern of primordia in the meristem. Pin1 protein is an auxin transporter,
driving efflux across the plasma membrane into the extracellular space. Each plant module grows
from a set of primordia in a meristem. (primordia is an organ/tissue in its earliest recognisable
developmental stages)
Where auxin accumulates in the root tips, auxin-responsive TFs perceives this and this activation
leads to the accumulation of PLETHORA (TFs), forming a gradient which regulates the activation of
genes involved in cell division and growth and it represses genes involved in cell differentiation.
Lecture 3: Morphogen gradients and axis formation
To understand how a developmental axis is created, we need to understand how to create different
cells along a particular dimension.
Genetic screens were used to discover and define groups of genes needed for early development
A fate map tracks how cells contribute to an organism, they are made by labelling living cells and
following them over time.
Maternal effect genes are required for normal embryogenesis in offspring. Maternal effect TFs
establish gradients which specify an axis A/P and D/V. Homozygous mutant females are viable but
produce no offspring, geneticists keep mutation by selecting heterozygotes. (mother provides
encoded protein to embryos to specify segment identities)
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