Development of the CNS Flashcards
1
Q
Define the process of gastrulation
A
Formation of 3 layers of endoderm, mesoderm and ectoderm from the 2 layers of epiblast and hypoblast
2
Q
Neural tube: explain how the neural tube develops
A
Early development of the CNS
- Transverse section through the embryonic disc around 3 weeks
- The first thing that happens is that you get a proliferation of the ectoderm in the dorsal midline of the embryonic disc
- This proliferation is called the neural plate
- As this thickens, the neural plate starts to fold up on the sides
- Eventually the two neural folds fuse dorsally to form a tube
- The space in the middle of the tube is called the neural canal
- You get a little bunch of cells at the tip of the neural fold called neural crests
- The neural crests separate from the neural tube and doesn’t take part in the fusion but lies alongside it
- At the end of this process you have a neural tube lying in the midline dorsally in the embryo and on either side of this you have two strips of neural crest tissue
- The neural tube and the neural crest are two independent sources of nervous tissue
Neural Tube = all CNS cells
Neural Crest = all PNS cells
The wall of the neural tube is called the NEUROEPITHELIUM
Differentiation of Neuroepithelium
- THREE types of cell comes from neuroepithelium
Neuroblasts
- All neurons that have their cell bodies within the CNS
Glioblasts
- These become neuroglia - astrocytes and oligodendrocytes
Ependymal Cells
- Lining ventricles and central canal
- These remain close to the inner membrane of the neural tube and they spread out and form a lining around the developing ventricular system
NOTE: neuroblasts include motor neurones because they have almost all their axons in the PNS but their cell bodies are in the CNS so they come from the neuroepithelium
3
Q
Neural crest cells: explain the term neural crest cells and recall examples of their development fates
A
- You get a little bunch of cells at the tip of the neural fold called neural crests
- The neural crests separate from the neural tube and doesn’t take part in the fusion but lies alongside it
- At the end of this process you have a neural tube lying in the midline dorsally in the embryo and on either side of this you have two strips of neural crest tissue
- The neural tube and the neural crest are two independent sources of nervous tissue
- Neural Tube = all CNS cells
- Neural Crest = all PNS cells
- The wall of the neural tube is called the NEUROEPITHELIUM
• Sensory neurones of dorsal root ganglia and cranial ganglia
Differentiation of Neural Crest Cells
- Postganglionic autonomic neurones: Sensory neurones of dorsal root ganglia + cranial ganglia
- Ganglia roots out in the periphery mediating autonomic functions – come from neural crest cells
- Schwann cells (myelin forming support cells of the PNS)
- Non-neuronal derivatives e.g. melanocytes
NOTE: A common feature of neural crest derived cells is that they are capable of migrating over quite large distances
- NB: a shared characteristic of all neural crest cell derivatives is their capability of migrating long distances (in order to reach the periphery) Differentiation of the neural tube into layers A cross section through the neuroepithelium shows initial symmetric proliferation of cells. Eventually, there is asymmetric cell division and differentiation of the daughter cells…
- The cell ready to undergo mitosis contracts down towards the inner membrane of the neuroepithelium, and then undergoes mitosis to form two identical daughter cells
- One of the daughter cells then remains attached to the inner membrane, and eventually returns
4
Q
Outline the proliferation and differentiation of the neuroepithelium
A
Proliferation of Neuroepithelium
- This is a cross-section of the wall of the neural tube at an early stage
- There is an inner membrane at the bottom and an outer membrane at the top
- Almost all these cells are attached to BOTH the inner and outer membranes - it’s just that the nuclei are in different positions
- The fat cells at the bottom are going through mitosis
Differentiation of Neuroepithelium
- Firstly, you get the cells withdrawing from the outer membrane towards the inner membrane and then it goes through mitosis
- One of the daughter cells will stay attached to the inner cell membrane, it gets bigger and goes into the cell cycle again
- The other daughter cell migrates away from the inner membrane and then develops into neuroblasts
- They develop processes (one will become the axon) and these axons are directed away from the inner membrane again
- As this occurs over and over you end up with THREE layers
- Ependymal layer – all developmental cells (where we find the ventricles -> These will migrate in grey matter in a laminar fashion
- Grey mater
- White mater- myelinated axons
- There is one layer by the inner membrane where you get mitosis occurring, another layer where you mainly have cell bodies and another that has mainly axons
- This is the beginning of the difference between grey and white matter
- Glioblasts also show a similar pattern of differentiation and migration to neuroblasts but glioblasts can migrate into WHITE matter as well
- REMEMBER: glioblasts DO NOT develop axons (but do develop processes)
- Ependymal cells just remain in the ependymal layer
Control of differentiation
- down to a host of signalling molecules(sonic hedgehog) produced by the range of tissues surrounding the developing neural tube.
- Signalling molecules secreted by surrounding tissues interact with receptors on neuroblasts
- Control migration and axonal growth by attraction and repulsion
- Depends on concentration gradient and time of secretion: the target cells have to have reached a certain stage of development in order to respond to the signalling molecules.
5
Q
Outline the layers of the Neural Tube in Cross-section
A
- The ependymal layer surrounds the neural canal
- The names in the brackets are the correct embryological terms
- The roof plate and the floor plate are landmarks that show the most dorsal and the most ventral parts of the canal
- This whole process of differentiation and migration is controlled by signalling molecules that are secreted either from the tissues surrounding the developing neural tube or sometimes secreted by cells within the neural tube
- These signalling molecules interact with receptors on the developing neuroblasts
- These signalling molecules also guide the developing axons
- The signalling molecules can either cause attraction or repulsion and the direction is determined by the concentration gradient - close to the source of the signalling molecules there will be a higher concentration
- The other important factor is TIMING - there is no point producing signalling molecules if the developing neurones don’t have the right receptors
- Some of the signalling molecules have different effects at different stages of development
- Important Factors: Concentration & Timing
6
Q
Spinal cord: summarise the cellular basis of formation of the ependymal, grey matter and white matter regions of the spinal cord, and separation of the grey matter into sensory and motor areas
A
- DEVELOPMENT OF THE SPINAL CORD In the basic layout of the neural tube, there are three layers (ependymal, grey and white). With the development of the spinal cord, there is increased proliferation of the layers
TWO significant features:
- The neural canal is even smaller compared to the thickness of the wall
- The grey matter has split into TWO different types:
- Alar Plate - Dorsal
- Basal Plate - Ventral
The interneurons in the alar plates are becoming specialized to receive sensory information and this information comes from the developing dorsal root ganglia that have developed from the neural crest
In the basal plate you get some interneurons and the development of motor neurones
This means that the basal plate has a motor function - the axons leave the spinal cord to go towards muscles
At the same time, the neural crest tissue on either side will develop into sensory neurons as the dorsal root ganglia. In the mature spinal cord, the alar plates are called the dorsal horns and the basal plates are the ventral horns.
Mature Spinal Cord
- The neural canal has become the central canal carrying CSF
- Alar plates develop into the dorsal horns
- Basal plates develop into ventral horns
- The whole spinal cord is surrounded by a thick layer of white matter
Dorso-ventral Patterning
- The notochord is found just below the basal plate in the developing neural tube (ventral)
- There are several signalling molecules being produced by the notochord and a concentration gradient is established with the highest concentration near the notochord
- The cells within the neural tube that are closest to the source are induced to become MOTOR NEURONES (in the basal plates)
- At the same time you have many other signalling molecules produced by the ectoderm (dorsal to the neural tube)
- They also establish a concentration gradient and tend to inhibit differentiation of cells into motor neurones
7
Q
Brain development: explain how differential growth and flexures gives rise to development of the mature brain, and summarise how cerebral cortical layers form from the neuroepithelium
A
- Only the most anterior bit of the neural tube develops into the brain
week 4
- You get differentiation of the wall of the anterior neural tube to form THREE primary vesicles:
- Prosencephalon - future forebrain
- Mesencephalon - future midbrain
- Rhombencephalon - future hindbrain
The rest becomes the spinal cord
Over the next week, the most anterior vesicle divides in two and the third vesicle also divides in two
This produces 5 secondary vesicles
week 5
- You get an enormous expansion of the top part of the developing forebrain and this telencephalon will become the cerebral hemispheres
- There is less expansion in the lower part of the developing forebrain because that part becomes the diencephalon
- The developing midbrain doesn’t expand very much
- The developing hindbrain divides in two to becomes the pons and the medulla
week 8
- As development continues you get more and more growth of the wall of the neural tube
- The space within it has become smaller relative to the wall and this space becomes the ventricular system
- Coming quite late, you have the first development of the cerebellum - out- pouching from the back of the pons
8
Q
Discuss folding of the developing brain
A
- The vesicles aren’t in a straight line - there are THREE flexures
- The flexures are named based on their position
- As you go through development these flexures become exaggerated
- By 8 weeks, the telencephalon has got so big that it’s starting to move back and cover the diencephalon
9
Q
Analyse the development of the brainstem
A
- The brainstem is a tubular structure but in the middle of it you have a 4th ventricle
- The development of the 4th ventricle makes a mess of the tubular organisation
- In the region that becomes the brainstem, the first thing that happens is the development of the 4th ventricle
- The roof plate starts proliferating rapidly and the dorsal part of the brainstem expands laterally
- As the roof plate expands it pushes the alar plates aside so they are no longer dorsal to the roof plate - they are actually lateral to the roof plate
- This shows the very much expanded roof plate forming the 4th ventricle
- The cranial nerve nuclei within the brainstem that have a motor function tend to lie more medially (because that’s where the basal plates have ended up after the split)
- Motor = Medial
- Sensory = Lateral
- Autonomic = in between
10
Q
Discuss Development of the Cortex
A
Development of the Cortex
- The brain has a core of white matter with grey matter around the outside
- The grey matter consists of nuclei that have migrated from the inner membrane of the neural tube
- This is a view of the cross-section through the wall of the developing hemisphere
- The neuroblasts are proliferating near the inner membrane
- Some of the neuroblasts will stay in the middle and form the basal ganglia
- There are other neurones that then migrate towards the outer membrane
- This migration takes place by the neuroblasts attaching themselves to radial glial cells - these have their cell bodies anchored in the inner membrane and have a single long process that goes to the outer membrane
- The neuroblasts attach themselves to radial glial cells and climb up towards the outer membrane
- You get a wave of proliferation near the inner membrane and then a wave of migration towards the other surface and then one layer of the cortex is formed
- Then you get another wave of proliferation and another wave of migration forming the 2nd layer of cortex
- This continues until you have SIX LAYERS of cells within the cerebral cortex
- Each layer of cells has different types of cells with different functions and different connections
- There will be problems later on if something disrupts the production of these layers
11
Q
Explain the clinical result of abnormal development of the neural tube
A
- The nervous system develops fairly early in gestation - even before women realise they are pregnant. So antenatal and pre-conception advice is important to provide the best environment for developing the baby.
- There is ongoing research in its early stages about using stem cell differentiation to replace lost neurons, and about guidance mechanisms for axons to induce CNS regeneration
Developmental Disorders of the Nervous System
- Neural development involves several complex, timed processes
- This may be disrupted by genetic or environmental abnormalities - This occurs early in gestation
- Schizophrenia is caused by a malfunction of neural development
- Deficiency of folic acid can lead to spina bifida
- Development of the nervous system starts very early in pregnancy
- Degenerative conditions – inability to form new neurons
