Development of the Nervous System Flashcards
What are the 3 processes that occur in week 1 of development?
Fertilisation:
- When the sperm enters the ovum and the 2 sets of genetic material carried by the gametes fuses together
Cleavage:
- This occurs when the zygote divides by mitosis into 2 cells…and so on
- When the ball of cells contains 16 cells, it is called the morula
Implantation:
- The blastocyst begins to invade the endometrium and implant in the uterine lining
What is blastulation?
The process of of forming the blastocyst
It occurs when cells of the morula separate and differentiate into an outer layer of cells (trophoblast) and inner cell mass (embryoblast)
What are the 2 layers of the blastocyst?
Which one invades the endometrium?
- Outer cell layer is the trophoblast
- This goes on to form the extraembryonic tissue and contribute to the placenta
- Inner cell mass is the embryoblast
- This goes on to form the tissues of the embryo
- The trophoblast penetrates the uterine lining during implantation
What is the process that occurs during week 2 of development?
Bilaminar disc formation
- The embryoblast differentiates into 2 layers
- Hypoblast layer - cuboidal cells located adjacent to blastocyst cavity
- Epiblast layer - columnar cells located more dorsally
What cavities form within the hypoblast and epiblast layers?
- Primitive yolk sac cavity forms within the hypoblast layer
- Amniotic cavity forms within the outer layer of epiblasts
What is the process that occurs during week 3 of development?
Gastrulation
This is the process of forming 3 primary germ layers, which will give rise to all the tissues of the body
What is the first thing that forms in the process of gastrulation?
Primitive streak
- This is a linear band of cells formed in the epiblast at the caudal end of the embryo
- The primitive node is an expanded area at the cranial end of the primitive streak
- This has roles in laterality and formation of the notochord
How are the 3 germ cell layers formed during gastrulation?
- Cells of the epiblast detach and migrate towards the primitive streak
The cells ingress into the streak and then migrate towards the rostral end of the embryo
- The first layer of epiblast cells that migrate will displace the hypoblast and form the endoderm
- The second layer of epiblast cells to migrate will form the mesoderm
- The remaining layer of cells does NOT migrate and forms the ectoderm
What are the 3 different types of epidermal stem cells that arise from the ectoderm layer?
What do they give rise to?
Neural ectoderm:
- this gives rise to the CNS
- cells differentiate into neural progenitor cells to form the neural plate
Neural crest cells:
- these give rise to the PNS
- cells differentiate into sensory & autonomic ganglia, melanocytes, glial cells, Schwann cells and other non-neural derivatives
Epidermal ectoderm:
- gives rise to the epidermis and sweat glands
- epidermis includes hair, nails & tooth enamel
Where does the notochord originate from?
What is its function?
- The notochord is of mesodermal origin
- It is a signalling centre that signals the overlying ectoderm to thicken
- It induces the formation of vertebral bodies and the ENTIRE CNS
- It induces the formation of the neural tube - the precursor to the CNS
What is the process that occurs during week 4 of development?
Neurulation
- This is initiated by the notochord, which induces cells in the midline to thicken and form the neural plate
What is the neural plate and how is it formed?
What type of cells are found in the neural plate?
- The notochord signals to cells of the ectoderm that are more in the midline to thicken and form the neural plate
- The neural plate contains neural progenitor cells that are capable of giving rise to any structure within the CNS
What happens to the neural plate once it has formed?
- The edges of the neural plate elevate to form neural folds
- The neural groove results from the formation of neural folds
- The neural groove will deepen
How do the neural folds fuse together?
- The neural folds come together and fuse at the 4th - 5th somite level
- Fusion proceeds towards closure of the neural tube in a bidirectional manner
- This occurs in a cranial and caudal direction
- The only parts of the neural tube that remain exposed to the external environment are the anterior and posterior neuropores
When do the anterior and posterior neuropores closed?
What happens if they do not close?
- the anterior neuropore closes FIRST on day 25
- the posterior neuropore closes on day 28
- the neural tube is fully formed at day 28 post-conception
- If the neuropores fail to close or closure is delayed, this can lead to neural tube defects
What neural tube defects can result from failure of the anterior and posterior neuropores to close?
How are neural crest cells formed?
What change do they undergo and what will they give rise to?
- As the neural folds elevate, some of the cells dissociate and migrate away from the forming neural tube
- These neural crest cells reside between the neural tube and overlying ectoderm
- As neural crest cells approach the midline, they leave the neuroectoderm to enter the mesoderm
- They undergo epithelial-to-mesenchymal transition
- They will give rise to the autonomic and peripheral nervous systems
If migration of neural crest cells occurs in the trunk region, what will these cells differentiate into?
Dorsal pathway:
- NCCs enter the ectoderm and become melanocytes in the skin and hair follicles
Ventral pathway:
- NCCs differentiate into:
- sympathetic and enteric neurones
- sensory ganglia (dorsal root ganglion cells)
- schwann cells
- adrenal medullary cells
If neural crest cells migrate in the cranial region, what will they differentiate into?
NCCs that migrate in the cranial direction will differentiate into:
- ganglia and glial cells in the head and neck
- melanocytes
- odontoblasts
- parafollicular cells
What are the 2 types of segmental ganglia that form from neural crest cells?
Dorsal root ganglia:
- These contain the cell bodies of sensory neurones carrying information from the periphery to the spinal cord
Sympathetic chain ganglia:
- These are autonomic ganglia associated with the “fight or flight” response
What are the 3 layers of the wall of the neural tube and what do they contain?
Ventricular zone:
- This is the neuroepithelium which contains highly proliferative neural progenitor cells (NPCs)
- After cell division, the NPCs differentiate into neuroblasts and they migrate into the mantle zone
Mantle zone:
- This contains neuroblasts, which are the precursor cells to neurones
Marginal zone:
- Neuroblasts form axons, which extend into the marginal zone
- As the axons becone myelinated, the marginal layer becomes the white matter of the spinal cord
What are the 3 layers of the developing spinal cord?
Which layers form white and grey matter?
- The lumen (ventricular zone) is lined with neural progenitor cells
- NPCs differentiate into neuroblasts, which migrate into the mantle zone
- The mantle zone will form the grey matter of the spinal cord as it contains the cell bodies of neurones
- The axons extending from the cell bodies are found within the marginal layer
- The marginal layer forms the white matter of the spinal cord
What 2 “plates” are formed from the neuroblast cells in the mantle layer?
What fissures form as the plates enlarge?
Alar plate:
- formed by more dorsally located cells within the mantle layer
- this is the precursor to the dorsal grey horn, which contains sensory neurones
- as the alar plate enlarges, the dorsal median septum forms
Basal plate:
- formed by more ventrally located cells within the mantle layer
- this is the precursor to the ventral grey horn, which contains motor neurones
- as the basal plate enlarges, the ventral median fissure forms
What is the sulcus limitans?
A shallow groove that marks the division between the alar and basal plates
This is present throughout the entire length of the spinal cord
What is significant about the midline roof and floor plates of the spinal cord?
They DO NOT contain neuroblasts as they are crossing points for nerve fibres
The roof and floor plates are thin
At what spinal cord levels is the intermediate horn present?
- This is located between the dorsal (sensory) and ventral (motor) horns
- It is only present between T1 and L2
- It contains sympathetic neurones
What are the roles of SHH and BMP in spinal cord patterning?
- Both of these proteins induce cell differentiation
- SHH is produced by the floor plate and stimulates more ventral cells to form the basal plate
- BMP is produced by the roof plate and stimulates more dorsal cells to form the alar plate
How is the notochord involved in formation of the basal plate?
How is the basal plate formed and what will it become?
- the notochord secretes sonic hedgehog hormone (SHH), which signals to the floor plate
- the floor plate then becomes a signalling centre, which secretes more SHH to the surrounding tissues
- cells located closer to the floor plate receive higher levels of SHH and will form the basal plate
- cells in the basal plate will eventually become motor cells
How is the ectoderm involved in formation of the alar plate?
How does this form and what do the cells located here eventually become?
- the ectoderm becomes a signalling centre and secretes proteins BMP 4 and 7
- BMP 4 & 7 signal to the roof plate
- the roof plate becomes a signalling centre and secretes more BMP 4 & 7 to the surrounding cells
- the cells receiving high concentrations of BMP will form the alar plate
- cells in the alar plate will eventually become sensory cells
How are motor spinal nerves formed?
- the axons of the basal plate will break through the marginal zone
- these are motor axons that will form the ventral root of the spinal nerve
- this is carrying motor information to the muscles
How are sensory spinal nerves formed?
What happens to them once they enter the spinal cord?
- The dorsal root ganglia are formed from neural crest cells and give rise to 2 processes
- central process
- peripheral process
- the central process penetrates the alar plate
- this will ascend in the marginal zone, or end in the dorsal horn to synapse across the midline
- the peripheral process joins ventral nerve roots to form a spinal nerve
- this will innervate the skin and give sensation at that spinal cord level
How does the vertebral column grow relative to the spinal cord?
- the vertebral column grows at a much faster rate than the spinal cord
- in adults, the spinal cord ends around L1/L2 and the dural sac extends to S2
How and why does anencephaly occur?
- the anterior neuropore fails to close
- neuroepithelium continues to proliferate so there are protrudings from the surface of the embryo
- this neuroepithelium is damaged due to continued exposure to amniotic fluid
- apoptosis and necrosis occur so that at birth, the brain has failed to form
What are the 2 different types of spina bifida?
Spina bifida occulta:
- the spinal cord is covered by skin
- problems tend to arise from nerves being tethered to the skin or surrounding structures and being stretched
Spina bifida averta:
- meningocele occurs when the meninges are protruding through the skin
- myelomeningocele occurs when both the meninges and spinal cord are protruding through the skin
Why do neural tube defects (especially spina bifida overta) commonly lead to hydrocephaly?
- the spinal cord can become tethered and not able to freely move as a result of a NTD
- the tethering creates a pulling force on the cerebellum and brainstem, causing them to descend
- the cerebellum herniates through the foramen magnum
- this blocks the normal circulation of CSF, causing it to accumulate and increase the pressure within the cranial cavity
How is hydrocephaly as a result of NTD treated?
ventriculoperitoneal shunt
- fluid is drained from the ventricular system to the peritoneal cavity, where it can be reabsorbed
What are the 3 swellings of the neural tube that develop as it begins to bend at the rostral end?
- 3 swellings develop at the broad cephalic region of the neural tube, that will develop into the adult brain
- prosencephalon (forebrain)
- mesencephalon (midbrain)
- rhombencephalon (hindbrain)
- the neural tube located caudal to the rhombencephalon will develop into the spinal cord
What happens during week 5 of development?
the 3 swellings of the broad cephalic region of the neural tube develop into 5 swellings
What are the 2 structures that arise from the prosencephalon?
What do these go on to form?
Telencephalon:
- this is the “outer brain” that goes on to form the cerebral hemispheres
Diencephalon:
- this is the “inner brain” that goes on to form the thalamus, hypothalamus, epithalamus and subthalamus
What structures arise from the mesencephalon in week 5?
What do they go on to form?
- the mesencephalon does not further divide and remains as the mesencephalon
- this will go on to form the adult midbrain
What 2 structures arise from the rhombencephalon during week 5?
What do these go on to form?
Metencephalon:
- this goes on to form the pons and cerebellum
Myelencephalon:
- this goes on to form the medulla oblongata
What happens to the lumen of the neural tube as the 5 swellings develop?
the lumen of the neural tube remains and forms the beginning of the ventricular system and central canal of the spinal cord
Why do brain flexures form?
What are the first 2 flexures to form and where are they located?
- the brain grows and expands rapidly and bends ventrally as it develops, producing brain flexures
Cephalic flexure:
- this appears at the level of the midbrain as the neural tube begins to bend ventrally
Cervical flexure:
- this appears at the level of the junction between the rhombencephalon and the spinal cord
What flexure forms after the cephalic and cervical flexures form and why?
Pontine flexure:
- formed due to unequal growth of the CNS between the cephalic and cervical flexures
- the pontine flexure separates the rhombencephalon into the metencephalon and myelencephalon
What is the rhombencephalic isthmus?
- a deep furrow that separates the mesencephalon (midbrain) from the rhombencephalon (hindbrain)
- it forms as the brain vesicles continue to expand
What do the coloured arrows equate to?
What is the role of the sulcus limitans in the developing brain?
- it is the groove that separates the alar plate from the basal plate
- it exists throughout the entire length of the CNS in the neural tube
How does the myelencephalon differ from the spinal cord?
- the lateral walls of the myelencephalon (medulla) are everted
- the roof plate is much thinner
How do the alar and basal plates reorganise themselves during development of the myelencephalon (medulla)?
- the alar and basal plates reorganise themselves into nuclear groups
-
alar plate nuclear groups deal with afferent SENSORY information travelling towards the CNS
- located more laterally in the medulla
-
basal plate nuclear groups deal with efferent MOTOR information leaving the CNS
- located more medially within the medulla
- some cells of the alar plate migrate ventrally and settle to form the olivary nucleus
What happens to the alar and basal plates during development of the metencephalon (pons)?
- there is formation of nuclear groups from the alar and basal plates
- _M_otor nuclei are located more _M_edially
- some cells from the alar plate dissociate and migrate ventrally to form the pontine nuclei
- the marginal layer around the basal plate expands to produce a large area of white matter in the ventral pons
- this allows for connections between the cerebral cortex, cerebellum and spinal cord
What is the role of the rhombic lips in development of the metencephalon (cerebellum)?
Where do they form from?
- the dorsolateral parts of the alar plates thicken and bend medially to form the rhombic lips
- the rhombic lips continue to proliferate and get closer to each other in the midline as the pontine fissure deepens
- the rhombic lips fuse in the midline and compress to form the cerebellar plate
What happens to the IVth ventricle as the cerebellar plate is forming from the rhombic lips?
- IVth ventricle becomes compressed between the cerebellum and pons and is no longer visible
- once this space is closed, the lateral and median apertures form to allow CSF to escape the ventricular system at the level of the IVth ventricle
What happens to the pontine flexure as the cerebellar plate forms?
- as the rhombic lips proliferate and come together to form the cerebellar plate, the pontine flexure deepens
- it remains as part of the IVth ventricle
What happens to the lumen of the neural tube during development of the mesencephalon (midbrain)?
- the lumen of the neural tube in the region of the mesencephalon remains
- it becomes much narrower and forms the cerebral aqueduct, which connects the IIIrd and IVth ventricles
What forms from the alar and basal plates as the mesencephalon (midbrain) develops?
- the alar and basal plates form nuclear groups
- the alar plate forms the superior and inferior colliculi posteriorly
- the superior colliculi deal with visual information
- the inferior colliculi deal with auditory information
- some cells of the alar plate detach, migrate ventrally and settle anteriorly to form the substantia nigra and red nucleus
What develops from the marginal zone during development of the mesencephalon?
- the marginal zone (area of white matter) gives rise to the crus cerebri (cerebral peduncles)
- many white matter fibres travelling to and from the cerebral cortex pass through the cerebral peduncles, including the corticospinal pathway
What are the 4 different fibre types that can be found in both spinal and cranial nerves?
General somatic afferent (GSA):
- fibres carry sensory information from the skin and skeletal muscle spindles
General visceral afferent (GVA):
- fibres carry sensory information from the viscera and blood vessels
General somatic efferent (GSE):
- fibres carry motor information to skeletal muscles
General visceral efferent (GVE):
- fibres innervate smooth muscle of the viscera, intraocular muscles, salivary glands etc.
What are the 3 different fibre types that are only found in cranial nerves?
Special somatic afferents (SSA):
- fibres carry sensory information from the retina, auditory and vestibular apparatus
Special visceral afferents (SVA):
- fibres carry sensory information related to digestion (smell and taste)
Special visceral efferents (SVE):
- fibres innervate skeletal muscles derived from the branchial (pharyngeal) arches
During development of the forebrain, how are the developing hemispheres connected?
In what direction do they fold?
- the 2 developing hemispheres of the telencephalon are connected in the midline by the lamina terminalis
- the cerebral hemispheres fold downwards during development to obscure the diencephalon
Why is it thought that the entire diencephalon is of alar origin?
- the notochord, which secretes SHH to pattern the floor plate, ends before it reaches the diencephalon
- there is no floor plate in the diencephalon
- this means there is no SHH being secreted to tell surrounding cells to develop into the basal plate
What 3 swellings make up the developing diencephalon?
- the diencephalon appears as 3 swellings on the lateral walls of the neural canal (future IIIrd ventricle)
- thalamus (Th)
- hypothalamus (Hth)
- epithalamus (Eth)
- these 3 swellings will give rise to the diencephalon
What marks the division between the thalamus and hypothalamus?
What forms the roof plate and inferior boundary of the diencephalon?
- the hypothalamic sulcus marks the division between the thalamus and hypothalamus
- the roof plate of the diencephalon is the choroid plexus, which is responsible for producing CSF
- the inferior boundary of the diencephalon is the optic chiasm
What structures make up the telencephalon?
- The telencephalon consists of:
- cerebral cortex (grey matter)
- underlying white mater
- basal ganglia & associated structures
What structures is the telencephalon derived from?
- the cerebral cortex and underlying white matter are derived from the pallium
- the basal ganglia and related structures are derived from the subpallium
- the entire telencephalon, pallium and subpallium appear to be of alar origin
What are the first structures to develop in the telencephalon?
How are the lateral ventricles connected to the IIIrd ventricle?
- 2 lateral outpocketings form, which are connected by the lamina terminalis
- these are the future cerebral hemispheres
- the lateral ventricles (LV) within the hemispheres are connected to the IIIrd ventricle via the interventricular foramen (of Monro)
How does the hippocampus form and change in position during development?
- the future hippocampus develops from the archipallium
- this is a thickening of the wall of the hemisphere above the foramen of Monro
- the hippocampus begins medially and frontally and migrates to sit in the temporal lobes of the adult brain
Why is the floor of the developing telencephalon thicker?
What develops from this area?
- it is thicker due to the presence of ganglionic eminences within the subpallium
- these ganglionic eminences form the corpus striatum
- fibres arise that will form the internal capsule, which divides the corpus striatum into the caudate nucleus and the lentiform nucleus
What happens during development of the telencephalon that brings the thalamus in close proximity of the caudate nucleus?
the medial wall of the hemisphere and lateral wall of the diencephalon duse together
What happens during development of the telencephalon as the 2 cerebral hemispheres converge in the midline?
- the mesenchymal tissue between the 2 hemispheres forms the falx cerebri
- this is an extension of dura mater that separates the hemispheres in the midline
- the hemispheres continue to grow to form C-shaped lobes
What is the insula and how is it formed?
- the region of the hemispheres adjacent to the corpus striatum grows much more rapidly than other regions of the brain
- this leads to the frontal and temporal lobes expanding over the developing insula
- the insula is the region of cortex that does not grow as rapidly as other regions, so becomes hidden between the frontal, parietal and temporal lobes
Why does the brain not remain lissencephalic (smooth)?
- in the final stages of development there is massive expansion, which leads to the formation of convolutions called gyri
What is lissencephaly?
What other deformity often accompanies it?
- a genetic defect that results in the brain being smooth in appearance
- it is often accompanied by microcephaly (abnormally small head), but this is not always apparent at birth
- there are different ranges of severity, from seizures to mental retardation and complete paralysis
- this depends on the extent of “smoothness”
- it is typically not very compatible with life
What 3 white matter fibre bundles arise from the lamina terminalis?
Anterior commissure:
- connects the olfactory regions of each hemisphere
Corpus callosum (CC):
- connects the frontal, parietal and occipital lobes with each other
Fornix commissure:
- This connects the hippocampus anteriorly
- As the hippocampus is pushed into the temporal lobe, it drags the fibres of the fornix along with it
What 3 white matter fibre bundles develop on the posterior aspect of the brain later in development?
- posterior commissure
- habenular commissure
- optic chiasm
What are the 5 main C-shaped structures within the brain?
- caudate nucleus
- corpus callosum
- fornix
- lateral ventricles
- choroid plexus
How can the pallium, which gives rise to the cortex, be further subdivided?
Archipallium:
- located medially
- gives rise to the hippocampus
Neopallium:
- “new cortex” that gives rise to heavily folded brain cortex involved in higher order functions
Paleopallium:
- both components of the archipallium and paleopallium are seen in other species
How do cells behave in the neopallium?
there is cell migration within the neopallium, which leads to the formation of a 6-layered neocortex
What is the zone closest to the ventricular system in the 6-layered neocortex?
What type of cells are found here?
- the ventricular zone is closest to the ventricles, which is composed of neuroepithelium
- highly proliferative neuroepithelial cells are found here, which are progenitor cells that give rise to all other neurones that will form the mature cortex
How do the neuroepithelial cells in the ventricular zone of the neocortex form 6 layers?
- the neuroepithelial cells in the ventricular zone proliferate and migrate to an area just below the pia mater
- as other neuroblasts keep being produced, they will surpass the previously produced layer to settle in a layer further above
- the outermost regions of cortex contain the youngest neurones
- the older neurones are located closer to the ventricular system
Why are white and grey matter regions in the brain and spinal cord “flipped”?
- the axons of the neurones of the cortex extend inwards from the periphery
- the grey matter is in the periphery and the white matter (axons extending inwards) is more central
- in the spinal cord, the white matter is in the centre and grey matter is in the periphery
What do the archipallium, neopallium and paleopallium develop into?
Archipallium:
- future hippocampal formation and dentate gyrus
Neopallium:
- forms the 6-layered cerebral cortex
- take a slice anywhere through the cortex and a 6-layered formation will be seen
Paleopallium:
- future olfactory cortex
Where is the longitudinal fissure located?
What would be seen if it was stretched open?
- the longitudinal fissure separates the 2 hemispheres
- if it was stretched open, the corpus callosum becomes visible
- this is a bunch of white matter fibres that connects the 2 hemispheres
What are the functions of the precentral and postcentral gyri?
Precentral gyrus:
- located anterior to central sulcus and is the primary somatosensory cortex
Postcentral gyrus:
- located posterior to the central sulcus and is the primary motor cortex
What are these structures?
Central sulcus:
- divides the frontal and parietal lobes
Lateral sulcus:
- located between frontal, parietal and temporal lobes
Parieto-occipital sulcus:
- located between the parietal and occipital lobes
Calcarine sulcus:
- divides the primary visual cortex in the occipital lobe into a superior and inferior aspect
