Development of the nervous system Flashcards
The function of the nervous system is underpinned by a circuit, what is the main roles of this circuit?
- sensing changed in the external environment
- deciding what to do based on instinct and experience
- responding
Label the nervous system
Define Neurogenesis ?
Neurogenesis is the process by which new neurons are formed in the brain
Define differentiation?
Cellular differentiation is the process in which a cell changes from one cell type to another
What is formed in the first 18 days of neurogenesis?
- The notochord which is formed at the midline
- the 3 layers:
Outside
Ectoderm
Mesoderm
Endoderm
inside
- Neural plate develops from overlying ectoderm (neuroectoderm)
- Neuroectodermal percursor cells: neurulation
What happens in the first 18-20 days of neurogenesis?
- The neural plate folds inwards and forms the neural groove
- the floor plate is above the notochord and here the neural tube/plate closes
What happens in days 20-22 of neurogenesis?
- Neural cells present above the neural tube
- Anterior neural fold
- Neural tube closes completely which forms the central canal
What happens in day 22-24 or neurogenesis?
- Somites form all the way around the central canal
- this closes the area and produces the spinal cord
- Rhombenecephalon present on spinal cord
- sensory ganglion develop around spinal cord under rhombencephalon
What structures are essential for instructung nervous system formation?
Notochord
Floorplate
Roofplate
What is the anterior end of the nervous system?
The brain
What does the neural crest seperate?
Separated from neural tube and is a major component of PNS
All the development covered occurs in the first 24 days but over a 4 day span of time, when does the PNS form?
The PNS is later formed from plate opening a few days after day 24
Which structure is the precursor that gives rise to the entire nervous system?
The Neural plate
There is a high degree of patterning in the neural tube. Tell me some of these distinct features?
- Anterior/ Posterior (rostral/ Caudal) along the length of the tube
- dorsal ventral in cross section
- patterning is instructed by morphogens
Tell me about the anterior-posterior patterning?
Proliferation and segmentation generate the early spinal cord and 3 primary vesicles: brainstem, midbrain and forebrain
Name transient structures that instruct nervous system formation (sources of morphogens)?
Roofplate
Floorplate
Notochord
Which structure gives rise to the PNS?
Neural crest
label these 2 developments of the nervous system…
At 25 days development of the brain, what is present?
Neural tube
At 40 days development of the brain, what is present?
Midbrain
Hindbrain
Spinal cord
Forebrain
At 100 days development of the brain, what features start to develop?
Cerebellum
Pons
Medulla
At what age does the brain take form as we know it?
9 months
What part of the brain distinguishes humans from animals?
Why is this the case?
The size of the cortex, particuarly the frontal lobe.
The brain determine the person and makes us who we are.
The frontal lobe is where our personality is determined as it’s where we judge risk/ reward
What determines a neurons ultimate fate?
When and were its born
Whats drives differentiation?
Morphogen gradients
How do morphogens drive differentiation?
They bind to receptors to activate or repress sets of transcription factors
Transcription factors control programmes of gene expression
What do gene expression profiles determine?
identity
What factors determine the response of each cell?
The distance from the secreting cells (gradients)/ availability of ligand + presence of receptors determines response of each cell
What are Hox genes?
A family of transcription factors
They establish segmentation along the anterior-posterior axis
How do we know that cell fate can be induced?
- Took a graft of tissue from pigmented to non-pigmented amphibian embryo
- Secondary axis developed, mixed origin
- transplanted cells instructed host cells
- “Spemann-Mangold organiser” (1923, Nobel prize for Hans Spemann in 1935)
How do we know that cell fate can be induced?
- graft of tissue from pigmented to non-pigmented amphibian embryo
- secondary axis developed, mixed origin- transplanted cells intructed host cells
What do morphogens bind to and what does this do?
Morphogens bind to receptors to activate or repress sets of transcription factors
What do transcription factors control?
They control the programme of gene expression
What do gene expression profiles determine?
identity
What determines the response of each cell?
The distance from the secreting cells (gradients)/ availability of ligand + presence of receptor
One example of a gradient going wrong is the lack of Shh (sonic Hedgehog signalling molecule), what does this lead to?
Optic vesicles generated on dorsal side
Shh inhibition/ loss leads to loss of ventral identity; Synophthalmis (“cyclopia”)
Whats Shh?
Sonic hedgehog is a protein that in humans is encoded by the SHH gene
it is the best studied ligand of the hedgehog signalling pathway others being (DHH- desert hedgehog) and (IHH- Indian hedgehog)
It plays a key role in the development of animals from insects to mammals
In vertebrates it is involved in organogenesis, including growth of digits, and organisation of the brain
What is Neuroepithelium/ Neuroepithelial progenitor cells in neural tube?
What do they form?
Neural precursor cells which form the ventricular zone
What does the radial glia connect?
How does it divide?
The ventricular and pial surface, divide slowly and symmetrically
How do precursors divide in the ventricular zone ?
divide asymmetrically
What is the ventricular zone?
The innermost layer of neural tube: “transit amplifying cells”
When building the cortex, new progenitors and postmitotic neuroblasts are generated
During migration, where do the neuroblasts migrate to?
What do they form?
The pial surface
They form the marginal zone
Differentiate into neurons
What do newer neuroblasts migrate past?
Their older cousins
How is the cortex described as being built?
“inside out”
What does a neurons final location reveal?
Its birthdate
What organisation is produced from migration?
Columnar organisation
Not just neurons: origin of glia. what are they also generated from?
neuroepithelium
What happens to glioblasts over time?
- Either remain attached to lumen
- become ependymal cells (production of CSF)
- Move to the marginal layer and form astrocytes (maintenance and repair)
- Move to the marginal layer and form oligodendrocytes (myelination)
Developing cortex
What is born in ganglionic eminences?
Cortical Interneurons are born in the ganglionic eminences- these are transient structures
What happens when cortical interneurons are produced?
- The cells migrate outwards
- Migrate tangentially
When neurites grow out, what is established?
Axon and dendrites
In order for brains to be functional, what do they need to be?
Wired correctly
What does the function of the brain depend on?
Ordered circuits
Which of these statements is correct:
- Radial glia connect the pial and ventricular surfaces
- Interneuron precursors migrate along radial glia cells
- Radial glial cells divide symmetrically to generate transit amplifying cells
- The cortex is built inside out
- Neuroblasts migrate towards the pial surface
(% was % of people deciding in the cohort)
Whats a Progenitor cell?
A precursor cell that like a stem cell, has a tendency to differentiation into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its “target” cell
How do axons navigate?
- the route is pre-programmed
- Axons navigate via intermeidate targets
- Axons grow along other axons as guides
What is in place to help the process know the entire route as it sets out?
Growing process of axons uses cues/signals to help them navigate from place to place
They also piggy back along the way
What are the classes of guidance signals?
- Can be attractive or repulsive
- Can be short-range or long-range
How are guidance signals interpreted and what do they act via?
Interpreted by growth cone that responds accordingly
Act via concentration gradients
Give examples of guidance signals for the short and long range signals.
“Non-diffusable”: short range; substrate derived. ECM; or presented on target cells: Cadherins, ephrin’s
“diffusible”: can act as gradients; long range; netrin, semaphorins
How do we know about guidance signals?
Identified using explant, cell culture experiments and genetic studies
Give some examples of guidance signals?
Examples of guidance cues: cadherins, netrins, ephrin, semaphorins
How are these guidance cues sensed?
By growth cones
(described by Cajal in 1890 as a motile structure)
What are growth cones?
They are located at the tip of growing axons and dendrites
They are hand-like structures with receptors on the surface
They sense guidance cues
Pick the correct statement abut guidance cues directing axon pathfinding…
- binding to receptors
- signalling to the cytoskeleton
- acting in gradients
How do guidance cues and axon pathfiding work together?
Why do not all neurons cross?
Motor neurons never cross
Silt + netrin-1 find both of these as repulsive as they have different receptors that interpret the signal differently
Axon guidance summary
- Developing neurons are guided to their targets by attractive and repulsive cues
- Guidance signals act on growth cone to determine direction of growth
- Upon receipt of signal growth cone undergoes (actin) cytoskeletal changes to move forward or change direction
- Once direction determined, (microtubular) cytoskeletal changes enable laying down of axon in desired direction
- Targets are found and circuits formed
Synapse formation
refinement of connections is important in development e.g. the elimination of those not needed
Are all contacts worth maintaining?
- Some synapses are kept, other abandoned
- Neurotrophins and electrical activity determine final pattern of contacts
Adhesin molecules stabilise what?
formed connections
What is the role of the following…
- Presynaptic neurexins?
- Postsynaptic Neuroligins?
Presynaptic neurexins: organise the SV docking zone
Postsynaptic neuroligins: recruit PSD
What did Victor Hamburger discover about limb removal?
Limb removal results in reduced numbers of motor and sensory neurons in the chick spinal cord (1934)
Once ciruits are formed what regulates them?
- The target – continued release of trophic factors; activity
- Learning and memory
- Disease
