S1) Embryology of the Nervous System Flashcards
What is gastrulation?
process whereby the outer layer of the bilayer germ disc invaginates at the primitive streak to produce a three layered germ disc
In gastrulation, what are the 3 embryonic disc layers?
Ectoderm
Mesoderm
Endoderm
What does the ectoderm give rise to?
Becomes skin and neural tissue as well as neural crest
It is interesting to note the close relationship between the skin and the nervous system – many primitive animals have the entirety of their nervous system embedded in the skin
What does the mesoderm give rise to?
Heart, vessels, muscles etc.
The notochord is a crucial structure composed of endoderm. It induces the overlying ectoderm to invaginate and form the neural tube
What does the endoderm give rise to?
Gut including accessory organs
Describe the five steps involved in the formation of the neural tube in early embryonic development
⇒ Gastrulation produces the notochord
⇒ Notochord induces neurulation
⇒ Neurulation induces the neural plate
⇒ Elevation of lateral edges of neural plate
⇒ Neural folds gradually approach each other in the midline and fuse, producing the neural tube
What is neurulation?
process of formation of the neural tube
What is the role of the notochord during neurulation?
The notochord directs the conversion of the overlying ectoderm to neurectoderm
What does notochord become in adults?
The nucleus pulposus in the intervertebral discs.
What does the neural tube give rise to?
spinal cord, spine, brain, and skull
Describe the process of neurulation.
- Induced by the notochord
- Elevation of the neural folds
- Fusion of the folds in the midline at mid cervical level with reconstitution of the surface ectoderm
- When the folds fuse, neural crest cells detach and migrate to their ultimate destinations
- Neural tube zips up rostrally and caudally
The neural tube zips up rostrally and caudally. What can arise if there is failure in fusion in the rostral vs caudal end?
- Failure in the rostral direction can result in anencephaly
- Failure in the caudal direction can lead to spina bifida
What is a neuropore?
A neuropore is a region corresponding to the opening of the embryonic neural tube in the anterior/posterior portion of the developing prosencephalon
Defects in closure of the neuropores underlie serious and common birth defects of the nervous system.
What are neural tube defects?
- Neural tube defects are defects which result from failure of the neutral tube to close
- Failure can occur caudally or cranially
What are the results of the following:
- Cranial neural tube defect
- Caudal neural tube defect
- Cranial neural tube defect results in anencephaly
- Caudal neural tube defect results in spina bifida
Most of the length of the neural tube gives rise to the spinal cord.
In four steps, explain how the cauda equina forms
⇒ A 3 months, the spinal cord is the same length as the vertebral column
⇒ Thereafter, the vertebral column grows faster
⇒ The spinal roots must elongate in order to exit at their intervertebral foramen
⇒ Cauda equina is formed
How are the primary brain vesicles formed?
The rostral neural tube displays a number of swellings which will become the major parts of the adult brain.
During neural fold formation three primary brain regions can be distinguished.
Identify these primary brain vesicles
- Embryonic forebrain (prosencephalon)
- Embryonic midbrain (mesencephalon) mes-middle
- Embryonic hindbrain (rhombencephalon)
How are flexures formed in the embryological development of the nervous system?
Growth & development at the cranial neural tube exceeds available space linearly, so it must fold up to form flexures
Which two flexures are formed in the embryological development of the nervous system?
- Cervical flexure
- Cephalic flexure
Where are the cervical and cephalic flexures located respectively?
- Cervical flexure – hindbrain junction
- Cephalic flexure – midbrain region
The primary brain vesicle swellings will become further subdivided.
What does the Prosencephalon give rise to?
- Telencephalon → becomes most of cerebral hemisphere – remember as telo- refers to the end, as in telomere at the end of a chromosome
- Diencephalon → becomes thalamus, hypothalamus and optic nerve/retina – remember as this structure is paired (prefix di- as in two)
The primary brain vesicle swellings will become further subdivided.
What does the Mesencephalon give rise to?
Stays the same as the boundary between the fore- and hind brain
The primary brain vesicle swellings will become further subdivided.
What does the Rhombencephalon give rise to?
Metencephalon → Forms the pons and cerebellum (remember as prefix met- refers to ‘behind’ or ‘after’, since the cerebellum and pons sit ‘behind’ the cerebrum. A meta-analysis occurs after the main research has been finished
Myelencephalon → Forms the medulla (the prefix myelo- refers to spinal cord, which the medulla joins on to)
At 5 weeks of development, the three primary brain vesicles become five secondary brain vesicles.
Identify these
Identify the mature derivatives of the following secondary brain vesicles:
- Telencephalon
- Diencephalon
- Mesencephalon
- Metencephalon
- Myelencephalon
What is the fundamental relationship between sensory and motor systems?
Development is regulated by complex molecular cascades.
The pattern is:
– Motor structures tend to sit anteriorly (ventral) (I remember this as you ‘motor’ forwards)
– Sensory structures tend to sit posteriorly (dorsal)
This pattern exists due to the development of the basal (floor) and alar (roof) plates in the neural tube.
What induces the formation of the basal/floor plate?
The notochord inducts the ventral (anterior) portion of the neural tube to become the basal (or floor) plate
What induces the formation of the alar/ roof plate?
The alar (or roof) plate forms in the absence of influences from the notochord
What does the basal/ floor plate and roof/ alar plate arise from?
Basal/ Floor plate → gives rise to motor neurones
Alar/ Roof plate → gives rise to interneurones and sensory neurones
We see this fundamental pattern of the organisation of the nervous system in terms of sensory and motor.
What do we see in the spinal cord?
Dorsal roots are sensory whilst ventral roots are motor
Dorsal horn - contains sensory neurones
Ventral horn - contains motor neurones
The dorsal columns (a sensory tract) sit posteriorly whilst the corticospinal tract (motor) sits anteriorly
We see this fundamental pattern of the organisation of the nervous system in terms of sensory and motor.
What do we see in the medulla?
The lemnisci (sensory) sit posterior to the pyramids of the medulla (motor)
We see this fundamental pattern of the organisation of the nervous system in terms of sensory and motor.
What do we see in the midbrain?
The colliculi (sensory) sit posterior to the cerebral peduncles (motor)
We see this fundamental pattern of the organisation of the nervous system in terms of sensory and motor.
What do we see in the cerebral cortex?
The primary sensory cortex (sensory) sits posterior to the primary motor cortex (motor)
(same pattern, but slightly different reason)
How does the cauda equina develop?
- Initially, there is a one to one correspondence between cord levels and vertebral levels (the cord fills the entire vertebral canal)
- However, the spine grows faster than the spinal cord, particularly at the lumbar levels (remember how big lumbar vertebrae are compared to thoracic and cervical ones)
- Therefore, the lower portions of the cord are stretched, drawing out the cauda equina
It is known that neural tube defects can predispose to hydrocephalus. How can this occur?
- This may be caused by tethering of the spinal cord at the site of the defect
- Thus, as the spine grows the cord cannot move within the vertebral canal, resulting in the brainstem (containing the fourth ventricle) being pulled down through foramen magnum and becoming occluded
- There are other mechanisms at play as well
What is the role of the ventricular system?
The ventricular system cushions the brain & spinal cord within their bony cases
Compare and contrast the ventricular system in development and adults
- In development, it is a tubular structure of the developing CNS persisting as development proceeds
- In the adult, it is comprised of interconnected “reservoirs” filled by CSF, produced by cells of ventricular lining
Relate the secondary brain vesicles to their corresponding ventricle in the ventricular system
- Telencephalon → lateral ventricle
- Diencephalon → third ventricle
- Mesencephalon → cerebral aqueduct
- Metencephalon & myelencephalon → fourth ventricle
What is hydrocephalus?
- Hydrocephalus is a condition characterised by excessive accumulation of CSF in the brain
- Is is most common in newborns with spina bifida occur due to a blockage of the ventricular system e.g. tumour, infection
- In hydrocephalus caused by impairment of CSF drainage within the ventricular system, the sites*
- of ventricular dilatation must sit rostral to the site of stenosis*
How can hydrocephalus be treated?
Hydrocephalus is readily treatable by use of shunt
(put a tube as a shunt to the brain and then enter the enlarged ventricle. Then put an outflow valve which will control fluid flow, then place rest of tubing into GI tract (abdo cavity). This is where CSF will drain into and gets reabsorbed)
Explain the early organisation of the neural tube by describing its three layers
- Inner: neuroepithelial layer
- Intermediate: mantle layer (neuroblasts)
- Outer: marginal layer (processes)
What is the function of the roof and floor plates of the neural tube?
Roof & floor plates regulate dorsal & ventral patterning
Describe the modality of the alar and basal plates respectively
- Alar plate = sensory
- Basal plate = motor
What is spina bifida?
- Spina bifida is a type of neural tube defect occurring when the vertebrae don’t form properly around part of the baby’s spinal cord
- It arises from the failure of neural tube closure caudally
- ‘double spine’ – since two bony ridges are palpable either side of the midline where the dorsal portion of the vertebrae failed to fuse
Spina bifida can occur anywhere along the length of the spine.
What is the most common location?
Spina bifida most commonly occurs in lumbosacral region
What is spinal dysraphism?
Dys- meaning disordered, and –raph relating to the formation of a raphe (where tissues zip up in the midline)
Therefore it is a problem with the fusion of structures in the midline e.g. fusion of neural folds to make the neural tube/ fusion of dorsal elements of vertebral column/ skull to form back of spine/ skull.
Failure of the neural tube to ‘zip up’ (i.e. neural folds don’t fuse) in the cranial or caudal directions.
What is the failure of closure in the cranial/ caudal direction involve?
Why can this occur?
- Failure of closure in the cranial direction involves the brain (e.g. anencephaly)
- Failure of closure in the caudal direction involves the spine/spinal cord (classic spina bifida)
All of these disorders, have failure of development of the posterior vertebral arches at one or more levels
When there is failure of the neural tube to ‘zip up’ (i.e. neural folds don’t fuse) in the cranial or caudal directions, we find there is absence of the posterior vertebral arch. Why?
It appears that the neural tube is at least partly responsible for inducing the migration of the sclerotome from somites to form the posterior bony arch.
Hence an anomaly in the neural tube may lead to disordered formation of the posterior arch.
Identify a spectrum of disorders from most severe to least
Craniorachischisis
Anecephaly
Myelocoele
Myelomeningocoele
Meningocoele
Spina bifida occulta
What is Craniorachischisis?
Craniorachischisis (cranio- referring to head, rachi- referring to spine, schisis referring to a split (as in a schism)
• The entire neural tube remains open as neural folds have failed to close.
• Hence failure of both brain and spinal cord to form
• Incompatible with life
What is anencephaly?
- Anencephaly is a neural tube defect resulting in the absence of cranial structures, including the brain
- It results from the failure of neural tube closure cranially and is incompatible with life
(an- without, cephaly- brain)
• The cranial neural tube fails to close
• Hence failure of the brain to form
• These children may be born alive but do not live for long
What is Myelocoele AKA rachischisis?
Most severe type of neural tube defect affecting the spine
(myelo- relating to the spinal cord, coele- relating to a fluid filled cyst)
The spinal cord fails to develop (neural tubes fails to fuse together + neural folds fail to invaginate .: open raw area exposed to outside world) ( i.e. the lumen of the neural tube is exposed to the outside world), usually associated with a CSF filled cyst
These children frequently have neurological deficits and are susceptible to meningitis due to the presence of exposed neural tissue
Which 3 conditions appear to have normal neural tube, but there is a failure of development of the posterior vertebral arch?
- Myelomeningocoele
- Meningocoele
- Spina bifida occulta
What is myelomeningocoele?
Normal neural tube, but failure development of posterior vertebral arch .: spinal cord and meninges have herniated
A CSF-filled cyst containing the spinal cord
Transilluminates relatively poorly (due to [presence of solid tissue in the cyst)
These children may have neurological deficits (less likely/ severe)
Repair is necessary
What is Meningocoele?
Normal neural tube, but failure development of posterior vertebral arch
Presence of a CSF filled cyst
The cord is sited within the vertebral canal .: spinal cord is not displaced + is in its normal location hence not too bad neurological deficits.
Transilluminates brilliantly
These children tend to have a good neurological prognosis (spinal cord is not displaced)
However, the cyst will need repair as it does predispose to infection
(IGNORE RED INK ON PICTURE)
What is spina bifida occulta?
The only anomaly is the lack of the posterior vertebral arch
May manifest a sign such as a tuft of hair or a large naevus over the defect
Not associated with significant neurological problems due to normal spinal cord and don’t have fluid filled cysts. Just missing some of the dorsal arches of the vertebrae caused by failure of closure of dorsal arches of vetebrae - often due to problem with the dorsal sclerotome.
Occurs in about 10% of the population!
How can one diagnose a neural tube defect?
- Raised maternal serum α-fetoprotein
- USS
How can a neural tube defect be prevented?
Folic acid pre-conceptually (3 month) and for the first trimester reduces incidence by 70%
- *400 micrograms daily**, to be taken before from around 3 months before conception and until week
- *12 of pregnancy**
Folate supplement = decreased rate of neural tube defects
What do they say is the mechanism of action of folate in preventing neural tube defects?
The mechanism of action of folate in preventing neural tube defects is unknown, however it is known that folate deficiency also predisposes to palatal anomalies.
Maybe folate is important for the fusion of epithelial sheets?
Describe the location and function of neural crest
- Location: cells of the lateral border of the neuroectoderm tube
- Function: become displaced and enter the mesoderm and undergo epithelial to mesenchymal transition
What are neural crest cells?
A highly specialised population of cells that are a vertebrate innovation
Multifunctional, contributing to a wide range of tissues
How are neural crest cells derived?
Derived from the point at which the neural folds fuse when the surface ectoderm is reconstituted
They become detached from the ectoderm and then migrate to their distant targets
Identify cells which have derived from the neural crest
- All neurones whose cell bodies are in the peripheral nervous
system
• Primary sensory neurones in PNS
• Autonomic postganglionic neurones
• Enteric neurones
- Schwann cells (neurilemma)
- Cells of the adrenal medulla (these are after all specialised sympathetic postganglionic neurones)
- Melanocytes
- The leptomeninges (i.e. the arachnoid and pia, lepto- means thin)
- Head mesenchyme (vital for head development), which contributes to many tissues such as pharyngeal arches
Identify tissues receiving a significant amount from neural crest.
- Thymus
- Thyroid
- Parts of the heart (e.g. spiral septum - seperates truncus arteriosus into aorta and pulmonary trunk → has large contribution from neural crest cells)
- Parts of the teeth
As streams of neural crest cells migrate from the dorsal part of the embryo, defined populations become left behind at certain points. These points correspond from dorsal to ventral.
Identify them.
- The dorsal root ganglia (sensory neurones)
- The sympathetic ganglia (sympathetic postganglionic neurones)
- The preaortic ganglia (sympathetic postganglionic neurones that receive input from splanchnic nerves)
- The adrenal medulla (chromaffin cells, which are homologous to sympathetic postganglionic neurones)
- The gut wall - enteric nervous system)
Due to the large number of contributions made by neural crest, disorders involving these cells tend to have quite diverse manifestations.
Identify 2 conditions.
Di George Syndrome
Hirschprung’s disease
What is Di George syndrome?
- Immunodeficiency (due to involvement of the thymus)
- Facial anomalies (due to contribution of neural crest to facial development)
- Heart anomalies
- Hypocalcaemia (involvement of parathyroids)
What is Hirschsprung’s disease?
- Problem with neural crest migration to the gut wall and certain segments esp large intestine .: lack of enteric neurones in sections of the large intestine
- This leads to hypomotility and constipation
