lecture 4 Flashcards
Development of the nervous system
What is the most complicated object that we know of in the universe?
the mature nervous system (probably a wrong statement, but impossible to prove that it is wrong)
What is the nervous system grossly divided into?
- the central nervous system: brain and spinal chord
- the peripheral nervous system
What is the trilaminar embryo?
- flat three-layered disc of cells between amniotic cavity and the yolk sac
- ectoderm (from where the NS arises), mesoderm, endoderm
- occurs at around week 2
Where do we see the first signs of the nervous system?
- during the trilaminar embryo
- a patch of tissue on top of the ectoderm, termed the neural plate, starts to specialise and becomes neuroepithelium
What does the origin of the nervous system reflect?
Being from the ectoderm, it reflects that the skin used to be the main interface/sensory place - the connection between the inside and the rest of the world
What do we start to see at the 2-3 week stage?
- structures that could be recognised as organs
- formation of the neural tube
- invagination of neural plate: overlying ectoderm starts to fold downwards into the mesoderm and endoderm
- downward fold forms a groove and then walls of this groove fold over and touch forming a tube
- this ectodermally derived tube breaks free from the ectoderm and floats between mesoderm and endoderm
- this tube forms the central nervous system
How thick is the neural tube initially?
one cell thick
Is the tube hollow or filled?
hollow
Is there a gradient in the formation of the nervous system?
Yes.
There is a rostral to caudal gradient in the formation of the nervous system.
The rostral is older.
What conditions occur when neural fold closure fails?
- failure to zipper shut section 2 on the crown of the head results in anencephaly
- failure to close stage 5 properly (at the base of the spine) results in spina bifida
infants with spina bifida often have disturbed motor neuron function, e.g. in lower in limbs
What is segmentation of the neural tube?
- rostral end of neural tube starts to swell
- forms 3 distinct vesicles
- prosencephalon (forebrain)
- mesencephalon (midbrain)
- rhombencephalon (hindbrain)
- what’s left over becomes the spinal cord
What further segmentation of the neural tube occurs?
- prosencephalon splits: telencephalon (cortex) and diencephalon (deep in the cortex)
- rhombencephalon - 7 segments
- rest is spinal cord
- rhombencephalon splits into metencephalon and myelencephalon (pons and medulla)
- retinae form as optic vesicles from diencephalon
At this early stage, what is the brain?
- a series of thin-walled bubbles
What is the neural crest?
- cells at top of neural tube form neural crest
- migrate away from neural tube to form a wide range of structures
- appear to very primitive
What are the neural crest derivatives?
Peripheral nervous system
- dorsal root ganglia
- sympathetic and parasympathetic ganglia
- enteric ganglia
- schwann cells
Melanocytes
Muscle cartilage and bone of skull, jaws, face and pharynx
Dentine
How do neural crest cells migrate?
- from neural crest under skin
- to site of dorsal root ganglia
- from neural crest through somite sympathetic ganglia
- neural crest cells follow specific paths through the embryo
- worst case of neural crest migration failure is in people who just have a hole instead of a face
- more common mild failure = cleft palate - last few cells haven’t arrived to form the face right in the midline
- segmental structures
- some jump ship from vagus nerve to gut
What is enteric migration?
- neural crest cells come from vagus nerve and migrate to form a plexus in the wall of the gut
- this migration is the longest in the body and goes on for the longest period of time
What has occurred by 5-6 weeks of development in a human? (or 11.5 days in a mouse)
- most major nervous system components in place
- major nerves present
- start to have the scaffolding of the nervous system present
- still haven’t built a brain that’s really worth anything
In the early stages of development, how thick is the neuroepithelium?
- a single cell thick
- “brain” is largely empty space
What is the ventricular zone?
- neuroepithelium adds layers to generate cortex
- all new neurons born at ventricular surface (“ventricular zone”) which contains stem cells
- eventually start to differentiate
- move upwards towards the surface after formed
What is a stem cell?
- means by which a few cells give rise to entire nervous system (and tissues replace lost cells)
- self renewing indefinitely and undifferentiated
- daughter cell capable of differentiation into specialised cells
- strict definition:
- totipotent
- could also be:
- pluripotent
- multipotent
- unipotent
Where are cells located in the developing brain?
- stem cells located in the ventricular zone
- differentiated neurons migrate from ventricular zone to cortical plate along radial glial process
- this is where the active neurons are required
What are the ‘railroad tracks’ of the brain?
- radial glial
- no matter how thick the cortex develops, these cells have one process attached to the bottom of the neuroepithelium and one attached at the top
- span the width
What is induction? Give an example.
- signals between structures or tissues
- involves ligands and receptors
- signal induces a particular response (next stem in development)
- generating different types of neurons: a problem that is very difficult because you want the right sort of neuron in the right place in the brain
- some neurons are excitatory while others are inhibitory
- needs to be set up correctly at the developmental stage
- induction is the process whereby cells interact in the brain to plot their location and make decisions about what sort of cell is needed at that location
e. g. spinal cord organisation
- the spinal cord has a core of grey matter surrounded by white matter
- in the ventral part of the grey matter there are specialised cells which are the motor neuron
- these cells send their axons out into the peripheral nervous system and which control the action or regulation of your skeletal muscles i.e. movement
- these motor neurons are part of circuits: some of these circuits extend down from the brain/cortex, others are local (i.e. interneurons)
- we need to set up differences in which muscles are innervated in the ventral horn - distal muscles tend to be innervated by more lateral cells, proximal muscles by those more medial
- there is a lot of information required to make sure that the right cells are in the right location, expressing correct phenotype e.g. neurotransmitter
- sensory processing is in the dorsal horn
- topographic organisation means neurons controlling distal muscle are lateral
How does spinal cord development occur?
- roof plate
- neural tube
- floor plate
- notochord (major structural element in the embryo that later degenerates)
- wide range of signalling molecules important
- set up gradients that define topography
- TGF-beta family in roof plate
- sonic hedgehog, retionic acid, noggin and chordin in floorplate and notochord
- the notochord broadcasts/releases chemicals that set up gradients
- cells detect differences in concentration to determine their location
What is the role of the floor plate? How?
- floor plate induces ventral horn motor neurons
- sonic hedgehog released by notochord therefore at highest concentration in the floor plate
- they in turn release/broadcast sonic hedgehog which extends the gradient
- and in that gradient a set of neurons can decide that they are motor neurons
What happens if you remove the notochord from a chick embryo? or add an extra?
no notochord = no motor neurons
two notochords = second pair of motor neurons
How does induction of interneurons occur?
- interneurons appear just dorsal to motor neurons
- depend on a chain of inductive events that start with the notochord
- notochord to floor plate: sonic hedgehog (high)
- floor plate to motor neurons (sonic hedgehog [low])
- motor neurons to interneurons - Isl-1 expression, motor neuron factor
- interneurons: En-1 expression
layer upon layer of interaction that set the topography of the spinal cord
3 dimensional interaction
What is axonal growth?
- axon is a key feature of mature neurons
- not present when neurons first forms
- axon grows out to meet its target cell (like a long cable)
- axons have to somehow connect to the right target
- axons extend over distance of millimetres in embryo
- initial scaffold of axon tracts laid down by pioneer axons - other axons grow according to these pioneer axons
What is a growth cone?
- axon is “towed” into position by growth cone
- fan like structures
- growing tips of axons
- axon grows because the end of it is actively pulling on it forcing the neuron to supply the growing axon with membrane etc
- little self powered tractor that sits at the head of the developing axon
- has pretty sophisticated machinery inside it
- growth cone is dynamic structure of cytoskeleton
- growth cone steers and homes in on target due to diffusible and membrane bound signals
Is the brain fully developed at birth?
- no
- processes described here form brain by birth
- development not finished - continues for significant time
What is plasticity of the brain?
- brain not fully developed at birth
- connections must be refined (plasticity)
- activity in neural circuits a key to plasticity
- human visual system performs badly at birth
- has to integrate vision from both eyes
Describe postnatal visual development
- eye patch on one eye of a new born kitten
- remove after three months
- no functional vision from covered eye although neural circuitry is intact
- visual cortex is now devoted completely to uncovered eye
- caused by relative lack of input from covered eye
What are critical periods?
- vision refined during critical period (12 weeks in kitten, 10 years in humans)
- critical periods found widely, including higher functions (hearing, language, social interactions)
- due to changes in weight and presence of synaptic connections
