Week 1 Topic 1 / 2 Flashcards
What is Waddington’s epigenetic landscape?
A metaphor for development and how cells make “decisions” to arrive to their “fates”.
How the cells turn out is not random but depends on external influences and interactions between groups of cells, which instruct cells on their next developmental step.
An example is the neural induction where the neural plate is influenced by the mesoderm to develop into the nervous system.
What are the aspects of neuronal differentiation?
Morphology (Appearance)
Gene expression profile
Neurotransmitter type
Axon projections and connections
What are the developmental steps that lead to differentiation?
Neurogenesis - during which cell division occurs to generate neurons
Cell migration - when young neurons migrate away from the ventricular zone
Axonogenesis - when the neuron starts to develop processes, including an axon which grows out towards targets;
Synaptogenesis - when axons make contact with their target neurons or other structures
Cell death or pruning - when regressive events often occur, leading to the formation of the mature neuron
Describe the neural tube in more detail!
(Intersection)
The neural tube is divided into a ventricular zone, adjacent to the ventricle, which contains the cerebrospinal fluid, and a mantle zone, adjacent to the pial surface covered by the meninges.
It contains radial glial cells. Radial glial cells are elongated cells with a long process or endfoot on each surface. These are the progenitor cells of the nervous system.
What are radial glial cells and what do they do?
Radial glial cells are elongated cells with a long process or endfoot on each surface. These are the progenitor cells of the nervous system.
Radial glial cells divide repeatedly to expand the progenitor cell population, and some of these divisions give rise to a neuron shown by the shaded cell in the cartoon.
The cell divisions themselves, of the cell body, occur adjacent to the ventricular surface of the neuroepithelium.
Once the neuron is generated in such a cell division, it will migrate along the radial glial cell, using it as a guide towards the mantle zone. There, further differentiation of the neuron will take place, including extension of an axon.
What are the two main types of migration?
Radial migration
One example of this is the spinal cord in the neural tube, in which progenitors of cells migrate radially from the inside to the outside of the neural tube to generate neurons.
This type also occurs in the telencephalon, or forebrain, which will later form the cerebral hemispheres.
Cells that migrate radially, along radial glia, give rise predominantly to the neurons with long axons that project to other regions of the nervous system, and that use the neurotransmitter glutamate, called excitatory projection neurons.
Tangential migration
This type of migration also occurs in the telencephalon, neurons migrate orthogonal to the radial axis.
Neuronal progenitors migrate from the ventral telencephalon into the dorsal telencephalon, the developing cerebral cortex, and intermingle with the neurons which have undergone radial migrations.
These neurons give rise to neurons with short axons, which use the neurotransmitter GABA, called inhibitory interneurons.
What is the third type of migration that is mentioned in the lecture?
The third type of migration is the example of the neural crest cells. These cells split off from the ectoderm while neurulation is underway.
The neural crest cells migrate away from the forming neural tube to form elements of the peripheral nervous system.
(In particular, these are the dorsal root ganglia and sympathetic ganglia in the trunk, and the cranial ganglia of the head.)
What are the stages of axonogenesis?
Stage 1 - neurons are initially round blobs, post-mitotic neuron.
Stage 2 - neurons look radially symmetrical, with several neurites, or processes.
Stage 3 - one of these neurites becomes selected as an axon in a process of symmetry breaking. This axon will go on to grow out and extend towards its targets.
Stage 4 - the axon continues to grow and the dendrites start to grow out from the cell body.
Stage 5 - the dendritic tree becomes more elaborate with small protrusions, or dendritic spines, forming on the dendrites.
In vitro, the neurons can be seen to form a network.
How do the development of the axons and the dendrites happen?
Development of the axon and the dendrites proceed in parallel.
Growing axons are guided by molecules in their environment to their targets.
Axons eventually make contact with their targets, whether that is a neuron, a gland, or a muscle.
In the case of neuron-neuron synapses, these are most frequently made on dendrites, and in fact, the dendritic spines.
In case of a neuron-neuron connection, where do the synapses connect?
In the case of neuron-neuron synapses, these are most frequently made on dendrites, and in fact, the dendritic spines.
Synapses are sometimes made on the neuronal cell body itself – axosomatic – or on an axon – axoaxonic.
What is the pre-synaptic and the post-synaptic part?
The synapse is formed by the growing tip of the neuron to the left on the neuron on the right.
The neuron to the left is the pre-synaptic part, and the neuron to the right, the post-synaptic part.
Presynaptic axon connects to the postsynaptic dendrite, soma (cell body), or axon.
List the various molecules that play role in synapse formation throughout the process!
- Neuroligins and neurexins - They are transmembrane proteins that are expressed by the postsynaptic (neuroligins) and the presynaptic (neurexins) neuron.
They bind the pre- and postsynaptic parts of the synapse together, and serve as a focus for other proteins to cluster together to form the synapse.
- Cadherins and SynCAMs - These are molecules that help to consolidate synapse formation.
- After that the neuroligins and neurexins help gather the neurotransmitter vesicles in the pre-synaptic side. They also gather the scaffolding proteins and neurotransmitter receptors on the post-synaptic side.
What are the 2 types of synapses?
There are excitatory and inhibitory synapses.
Different members of the neuroligin groups are specifying these different synaptic types.
Neuroligin 1 specifies the excitatory synapses and Neuroligin 2 specifies the inhibitory synapses.
What are cell death and pruning?
Cell death and pruning may eliminate unwanted neurons or connections, match numbers of pre and post-synaptic cells, and ensure that synaptic transmission and circuit function is optimised.
It’s estimated that around 50 percent of motor neurons, for example, die during later development.
In the developing cortex of humans, the complexity of the brain can initially be seen to increase, in terms of the density and numbers of neurons, up to two years of age, with increasing synapse formation.
From four years to six years, however, a process of synapse pruning and consolidation takes place, and some decrease in the complexity of the brain landscape occurs. Pruning can occur to axons and to dendrites, which disintegrate and the debris is then cleared away.
Why do cell death and pruning occur?
It’s not completely clear why these events occur, but it may be to ensure that there are matching numbers of pre- and postsynaptic cells.
