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
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