L6. Development of the CNS Flashcards
Describe the basic principles of neuralation
Occurs after gastrulation at the tri-laminar stage where there are the three layers of cells (ectoderm, mesoderm and endoderm).
Cells at the centre of the mesoderm differentiates as a result of being under the primitive streak into the notochord.
The notochord then induces a change in the ectoderm above it to form a structure called the neural plate.
Neural plate cells dive into the mesoderm to form a ring-like structure that pinches together and zips up to become the neural tube.
What are the cells forming the neural plate referred to?
What do these cells eventually form?
The neuroepithelium
The neuroepithalial cells form the nervous system
Describe the neural tube
Is a hollow tube
Comprised of a thickness of only one layer
Where is the site of neural fold closure?
The centre or middle of the tube closes outwards towards the base of the neck and towards the base of the spine
What is meant by the rostral to caudal gradient in the formation of the nervous system?
The timing of the fusion of the neural tube is not the same along the length of the neural tube,
The rostral end (anterior) is older (it fuses before) than the caudal ends.
This is important to the the formation of the rest of the CNS following this stage
Describe the distinct stages in neural fold closure in terms of the embryo [5]
- The middle of the tube zippers up to the neck and to the base of the spine
- The crown then zips up towards the forehead and back of the skull
- The face and forehead zip up from below
- The base of the neck zips to the back of the skull
- The caudal end of the embryo zips up to the base of the spine
Describe 2 examples of disorders that can occur as a result of the failure of the neural fold closure
- SPINA BIFIDA occurs when there is a failure in closure of the caudal end of tube - step 5 (leaving a part of the nervous system exposed at the back)
- ANACEPHALY is a deadly disorder where failure of closure of the crown of the embryo occurs - step 2. This leaves the top of the head open and bathing in amniotic fluid and failure and disorganisation in developing the brain and skull.
What is the next step in neural tube development after closure?
This totally hollow tube at this stage (still one cell thic)
Rostral end of neural tube starts to swell and form 3 distinct vesicles. These vesicles go on to form the brain and the remainder of the tube becomes the spine.
What are the three major vesicles that are formed in segmentation of the neural tube?
(Note: don’t really need to know the names just the consequences)
- Prosencephalon (forebrain)
- Mesencephalon (midbrain)
- Rhombencephalon (hindbrain)
The Prosencephalon (forebrain) undergoes further segmentation into 2 major parts. What are these parts and what do they become?
Telencephalon: cortex and basal ganglia
Diencephalon: thalamus and hypothalamus
The telencephalon further splits into 2 parts (left and right). What do these form?
The right and left cerebral hemispheres
The rhombencephalon (hindbrain) also undergoes further segmentation into further parts. What do these parts form?
(Note: don’t need to know the names just the end result)
Pons and Medulla
Describe the formation of the retinae
Retinae forms as outgrowths of the brain (additional vescicles formed by the segmentation) that has been pushed out and is connected back to the origin by what becomes the optic nerve.
Describe the formation of the neural crest
As the neural fold closes in on itself to form the neural tube, a few cells from the ectoderm spill out and migrate away to form the neural crest
What is the major structure(s) formed by the cells of the neural crest?
THE PERIPHERAL NERVOUS SYSTEM
- Dorsal Root Ganglia
- Autonomic Ganglia (symp and parasymp)
- Enteric Ganglia
- Schwann Cells
(also melanocytes, muscle/cartilage/bone of the skull, jaws and face, pharynx, dentine)
Desribe neural crest migration
What is the significance of this in terms of pathology?
Cells of the neural crest have to migrate from their site to under the skin or to the site of the DRG and sympathetic ganglia (which is a potentially long way to go).
Because they have a long distance, there is a lot that can go wrong with their travels and lead to developmental and birth defects
What is the longest path that is needed to be taken by the neural crest cells?
The longest path is to form the cells of the enteric nervous system. Cells need to travel via the oesophagus down the elongating gut tube to populate the enteric nervous system.
This is stretching the migratory capacity of the cells and thus very little needs to happen in order for the process to go awry
Describe the neuroepithelium of the neural tube in terms of
- Cell layering
- Cell morphology
- Polarity of the cells
The neuroepithelium is a single cell layer thick that encloses a very large fluid filled space (otherwise hollow)
The cells are elongated and arranged in long and thin parallel strands of cells, each spanning the whole length of the layer.
The cells have a ventricular surface (lining the lumen or future ventricles) and an apical surface (beneath the ectoderm)
What is the preferred site of division of stem cells of the neuroepithelium?
Describe how this process of division occurred
The ventricular surface
The neuroepithelial cells would break their connections with the outer surface and shrink down into almost circular shaped cells at the base (ventricular surface).
They would then divide and the daughter cells would elongate and reattach themselves as long stretched cells once again.
How does the generation of the cortex occur? (Describe how the layering of the cortex arises)
As more and more cells begin to emerge from the division of stem cells in the ventricular zone the cells begin to DIFFERENTIATE.
There is a radial migration of the daughter cells from the ventricular surface outwards towards the skin (top layer) where they are laid down).
This constant addition of cells from the innermost side of the brain to the outemost creats the layering down of distinctive layers of the cortex.
As the cortex thickens by this process of stem cell division and migration to the top, the migration distance becomes very long. How do cells know where to go and where to stop?
A population of the neuroepithelial cells maintain the connections on both the surface and the ventricular sides of the growing cortex from the beginning.
These are called radial glia
They act as a railroad track and direct new cells to the top. (They also have their own stem cell population)
Describe 2 examples of developmental disorders that can occur if there are errors in the migration and differentiation processes of the neuroepithelium
Problems with these processes cause profound mental retardation.
- Reelin Mutation: The molecules that are meant to guide, stimulate and direct the cells in migration are mutated and dysfuncational causing a disorganised layering of the cortex
- Lissencephaly (Doublecortin, DCX gene): Causes no organisation in migration leading to little distinction between white and grey matter and very large ventricles.
How is cell identity assigned to the migrating cells of the neuroepithelium?
By a process of induction.
Signals pass between structure or tissues through ligand and receptor signalling to induce particular responses to the cells (to tell them what the next step is in development)
The CNS is organised in a very complex way with a large number of different neurons, each requiring different pathways, target cells and signalling processes.
What is the main concept that underlies the development of the different types?
Induction
The physical presence of a cells in that microenvironment and the signals it is receiving from its neighbours is the major factor
