Development of the CNS Flashcards
When is the embryo particularly prone to damage by the environment
The 3rd trimester
What essentially forms the CNS
The folding of the neural plate
What is the initiation of neural development dependent on
The cells that will generate the nervous system become distinct early in the generation action of a vertebrate embryo, concurrent with the establishment of the midline and the basic body axes: anterior-posterior (mouth-anus), dorsal-ventral (back-belly), and medial-lateral (midline-periphery). These axes are foundational for proper generation of every organ in the body, including the brain. In addition, the unique curvature of the human CNS generates a distinctive rostral-caudal axis in the developing brain. The axes, and thus the initiation of neural development, are critically dependent on the process of gastrulation.
Describe gastrulation
Gastrulation begins as the local invagination of a subset of cells in the very early embryo (which starts out as a single sheet of cells). By the time invagination is complete, the embryo consists of 3 layers of cells called the germ layers: an outer ectoderm, a middle mesoderm (these cells initiate the invagination that defines gastrulation); and an inner endoderm.
What determines the midline and different axes of the embryo
Based on the position of the invaginating mesoderm and endoderm, gastrulation defines the midline as well as the anterior-posterior and dorsal-ventral axes of all vertebrate embryos. These axes will determine the position of all organ systems including the peripheral and CNS, as well as facial structures and appendages
When does the development of the nervous system begin
At approximately 3 weeks gestation. At this point the embryo consists of 3 layers:
endoderm (forms G.I tract amongst other things)
mesoderm (forms muscles, connective tissues and blood vessels)
ectoderm (forms the entire nervous system and the skin)
What are the walls of the neural tube lined by
the neuroepithelium- whose cells give rise to the CNS
Summarise the process of early development of the nervous system
§ At approx. 3 weeks you get the transverse sections on the left.
§ There are 3 distinct layers – ectoderm, mesoderm and endoderm.
1. There is a proliferation of the ectoderm to form the neural plate.
2. As this thickens, the neural plate folds up on the sides and eventually fuse dorsally.
a. The space this leaves is called the neural canal.
3. A little strip of cells at the dorsal tip of the neural fold form the neural crests that run alongside the neural canal more dorsally.
a. Neural tube = all CNS cells (the wall of the neural tube is the neuroepithelium).
b. Neural crest = all PNS cells.
Describe neurulation
At around day 22 of gestation, an area of ectoderm on the dorsal surface of the embryo, called the neural plate, thickens and folds to form the neural groove. The ridges on either side of the groove expand and begin to fuse in the midline approximately halfway along its length (at the level of the fourth somite). Somites are paired blocks of mesoderm segmentally arranged alongside the neural groove of the embryo. The very tips of these ridges become the neural crest, and the fused neural tube gives rise to the brain and spinal cord (CNS)
When do the tubes at each end fuse
The tube at the cranial (rostral or head-end) neuropore fuses on day 25, and the caudal (tail-end) fuses on day 27.
Summarise the neural crest cells
the neural crest cells give rise to most of the cells in the PNS (including the dorsal root ganglia) along with cells of the autonomic ganglia, adrenal medulla and melanocytes in the skin. Dorsal root ganglia send their developing axons into the developing spinal cord and also towards the periphery. The advancing growth cones of these neuronal processes are guided to their appropriate central and peripheral targets by means of diffusible neurotrophic factors and cell adhesion molecules.
By the end of development, where is the segmental arrangement of the nervous system retained
By the end of development, the segmental arrangement of the nervous system (as determines by the somites) is retained only by the spinal cord.
Describe the differentiation of the neuroepithelium
o Neuroblasts – all neurones with cell bodies in the CNS.
§ Includes upper motor neurones as cell bodies in CNS but lower MNs in PNS.
o Glioblasts – (become neuroglia) astrocytes and oligodendrocytes.
o Ependymal cells – lining ventricles and central canal.
§ Remain close to inner membrane of neural tube.
What is a central event for the development of the nervous system
The formation of the notochord in the midline of the gastrulating embryo.
The notochord is a distinct cylinder of mesodermal cells that condenses at the midline as the mesoderm invaginates and extends from the mid-anterior to the posterior aspect of the embryo. It is generated at a site of a singular surface indentation called the primitive pit, which subsequently elongates to form the primitive streak. As a result of these cell movements, the notochord defines the embryonic midline and thus the axis of symmetry for the entire body
What happens to the notochord
The notochord itself is a transient structure, which disappears once early development is complete. The notochord specifies the basic topography of the embryo defining the midline and axis of symmetry, determines the position of the nervous system, and is required for subsequent early neural differentiation.
Describe the role of the notochord in neural differentiation
Along with cells that define the primitive pit, the notochord sends inductive signals to the overlying ectoderm that cause a subset of cells to differentiate into neuroepithelium precursor cells.
What do the neural crest cells differentiate into
§ Neural crest cells – 4 types of cells differentiate from the neural crest cells:
o Sensory neurones of dorsal root ganglia and cranial ganglia.
o Postganglionic autonomic neurones.
o Schwann cells – myelinate axons in PNS.
o Non-neuronal derivatives – e.g. melanocytes- pigment cells in the skin
Describe the proliferation of the neuroepithelium
§ This is a cross-section of the neural tube at an early stage.
§ There is ONE-layer of cells (it just doesn’t look it as they’re squished) and most cells are attached to both the inner and outer membrane.
§ The bigger cells towards the inside are undergoing mitosis.- inner cells show massive proliferation- lots of mitosis occurring here (seen in histology of cells)
Summarise the migration of cells in the neuroepithelium
§ Once the cells have finished mitosis at the inner membrane, one daughter cell migrates to the outer.
§ At the outer, the cell develops into neuroblasts.
§ The cells develop dendrites and then axons directed away from the inner membrane.
§ Eventually you end up with 3 layers – inner membrane layer with mitosis occurring, another with neuronal soma, and another with axons.
o Defines grey (soma) and white (axons) matter.
In what manner do the cells migrate
In a laminar fashion
Where are the ventricles found
The ependymal layer
Describe how the neuroblast cells of the neuroepithelium (neural tube) differentiate
The neural tube contains neuroblast cells. its hollow centre becomes the spinal canal. Neuroblasts adjacent to the canal divide and travel to the outer mantel layer, ultimately forming the neurons of the grey mater of the spinal cord. These neuroblasts/neurons project nerve fibres that grow outwards into the marginal zone, ultimately forming the white mater of the spinal cord.
Summarise the differentiation of the glioblasts and ependymal cells
Glioblasts show a similar pattern of differentiation but can migrate to the white (axon) matter as well (Glioblasts do NOT develop axons, but do develop processes). Ependymal cells just remain in the ependymal layer.
Describe some of the mediators involved in the differentiation of the neuroepithelium
The cells at the ventral midline of the neural tube differentiate into a specialised strip of epithelial-like cells called the floorplate (reflecting their position at the ventral and medial part of the neural tube- above the notochord). Molecular signals from the floorplate as well as from the notochord specify position and fate for the neuroectodermal precursors of the spinal cord and hindbrain.
Where do the signals to differentiate come from in the forebrain
In the forebrain, non-floorplate ventral midline structures s well as neural-crest derived mesenchyme immediately adjacent to the prosencephalic vesicle provide similar signals.
As well as cell type what else do the neuroectodermal precursor cells determine
Eventually, subsets of the neuroectodermal precursor cells generate region- and fate-specified neural progenitors that differentiate into specific classes of neurons in distinct brain structures.
Describe how the neuroectodermal cells determine the migration of the cells
Signals from the floorplate, the somites, and the cranial neural crest for the forebrain lead to differentiation of cells in the ventral neural tube that eventually give rise to spinal and hindbrain motor neurones, closest to the ventral midline, or basal forebrain structures as well as related interneurons, once again closest to the ventral midline.
Precursor cells further away from the ventral midline give rise to sensory realy neurons and related interneurons in more dorsal regions of the spinal cord and hindbrain.
What is the differentiation of the dorsal cell groups facilitated by
A narrow strip of neuroepithelial cells at the dorsal midline of the neural tube referred to as the roofplate of the spinal cord.
Like the notochord, the floorplate and roofplate are transient structures that provide signals to the developing neural tube and all but disappear once initial nervous system development is complete
Summarise the layers and differentiation of the neural tube
§ There are 3 clear layers:
o Inner – Ependymal layer – germinal layer.
o Middle – Grey matter – mantle layer.
o Outer – White matter – marginal layer.
§ The process of differentiation is controlled by signalling molecules secreted from surrounding tissues that bind with receptors on neuroblasts.
§ These control migration and axonal growth by attraction and repulsion.
§ Differentiation then depends upon concentration gradient and timing.
o Concentration gradient – close to source of molecules = higher conc.
o Timing – only produce s. molecules when developing neurones have the correct receptors to receive them.
What ultimately controls differentiation
Selective signalling molecules- which determine how far and where the cells migrate to in their development- as well as what they develop into.
Trophic and inhibitory signals present
Describe the sonic hedgehog
Peptide hormone essential for induction in the developing nervous system. Particularly important for 2 phases:
closing the neural tube, especially the anterior midline, and establishing the identity of neurones- in the ventral portion of the spinal cord and hindbrain.
The transduction of signals via the sonic hedgehog requires the cooperation of two surface receptor proteins, patched and smoothened.
How does the arrangement of white and grey mater differ in the brain and spinal cord
Spinal cord- white mater is the marginal layer
Opposite in the brain
Summarise the developing spinal cord
Cross-section through neural tube later on in development. Two significant features:
§ Neural canal is much smaller than thickness of wall.
§ Grey matter is split into two distinct types:
o Alar plate – dorsal.
§ Receive sensory information.
o Basal plate – ventral.
§ Has some inter-neurones but also motoneurons to send information out of the ventral roots.
Describe the two populations formed by the neuroblasts in the primitive grey mater
Dorsal alar plate and a ventral basal plate separated by a shallow groove (sulcus limitans):
the alar plate forms the sensory cells and interneurons of the dorsal horn
the basal plate cells form the motor cells of the ventral horn along with sympathetic (thoracic) and parasympathetic (lumbar and sacral regions) preganglionic neurons
Summarise the control of differentiation
Control of differentiation: signalling molecules secreted by surrounding tissue interact with neuroblast receptors to control migration and axonal growth - depending on concentration gradient and timing (attraction and repulsion)
What does the mesenchymal tissue around the neural tube form
The mesenchymal tissue around the neural tube forms the coverings of the brain and spinal cord.
Compare the length of the spinal cord to the vertebral column throughout development
In the first 8 weeks of gestation, the spinal cord is the same length as the vertebral column. After 8 weeks the vertebral column grows at a faster rate. By 40 weeks of gestation (term), the spinal cord stops at the level of L3 and, in adults, it ends at L1. The spinal nerve roots below this level descend within the vertebral canal until they reach the appropriate exit foramen. The pia mater remains attached to the coccyx and, therefore, elongates with respect to the spinal cord. The strand of pia mater between the coccyx and the lower end of the spinal cord is known as the filum terminale, and collectively with the individual nerve roots below L1, as the cauda equina (literally ‘horse’s tail’).
Describe cauda esquina syndrome
A prolapsed intervertebral disc or fracture can cause compression of the cauda equina. The symptoms of this include pain in the nerve distribution of the root affected, saddle anaesthesia (around the anus) and disturbance of bladder/bowel function. It is a neurosurgical emergency and the pressure must be relieved to preserve the function of the nerves.
Which types of neurons do the alar plate and basal plate give rise to?
Alar plates- interneurons (receive sensory information)
Basal plates- motor neurones and interneurones
Describe the cell types that the neural crest cells give rise to
The neural crest cells give rise to most of the cells in the peripheral nervous system (including the dorsal root ganglia) along with cells of the autonomic ganglia, adrenal medulla and melanocytes in the skin. Dorsal root ganglia send their developing axons into the developing spinal cord and also towards the periphery. The advancing growth cones of these neuronal processes are guided to their appropriate central and peripheral targets by means of diffusible neurotrophic factors and cell adhesion molecules.
By the end of development, where is the segmental arrangement of the nervous system retained
As determined by the somites
In the spinal cord
Summarise the spinal reflex
Sensory info in via DRG
Single synapse to motor neuron in ventral horn- out to musculature
Describe the purpose of the interneurones
Sensory info from DRG- into interneurones in different pathways depending on the sensory modality (i.e pain and temp take a different pathway to touch and proprioception)
Summarise the mature spinal cord
Butterfly arrangement of grey mater
§ The neural canal à central canal and now carries CSF.
§ Alar plate develops à the dorsal horns.
§ Basal plate develops à the ventral horns.
§ Whole spinal cord becomes surrounded by a thick layer of white matter.
Neural canal is surrounded by ependymal cells
Central canal also shrinks
Describe dorso-ventral patterning
The notochord is found just below the basal plate (ventral side).
The notochord produces several signalling molecules and a concentration gradient is established with the highest concentration near the notochord.
o The cells within the neural tube closest to the notochord therefore are induced to become motor neurones (in basal plates).
The ectoderm (dorsal to neural tube) also produces signalling molecules and these also establish a concentration gradient but these tend to inhibit cell differentiation into motor neurones.
Summarise the development of the brainstem
The brainstem has the same basic structure as the spinal cord, except that it has to accommodate the large motor and sensory tracts that run between the spinal cord and the brain.
Describe the development of the medulla of the brainstem
Initially, the myelencephalon or medulla is organized like the primitive spinal cord with alar and basal plates. As it flattens out further up, forming the floor of the fourth ventricle, the alar plates (sensory cell groups) move outwards until they lie lateral to the basal plates (motor cell groups). Other cells from the alar plate migrate ventrolaterally to form the olivary nuclei.
Neural tube not closed here
What are the basal plates medial and alar plates lateral in the brainstem
early development occurs in a tubular fashion, similar to spinal cord, and lateral proliferation of the roof plate enlarges the canal to form the 4th ventricle - this causes the basal plate to lie medially and the alar plates laterally, dictating the pattern of cranial nerve nuclei
How are the cells of the alar and basal plates in the brainstem arranged
The cells of the alar and basal plates are arranged in columns according to whether they innervate somatic (body wall) or visceral (internal organ) structures:
•
The basal plate forms the motor nuclei for cranial nerves IX, X, XI, XII.
•
The alar plate forms sensory nuclei for cranial nerves V, VIII, IX, X along with the gracile and cuneate nuclei (receiving inputs from the spinal cord).
Describe the development of the pons
The pons is formed by the anterior part of the metencephalon and part of the alar plate of the medulla. It contains a thick band of fibres (important in motor processing) which connect the forebrain with the cerebellum. The neurons of the ventromedial alar plate at this level form: • The main sensory nucleus of V • A sensory nucleus of VII • Vestibular and cochlear nuclei of VIII • Pontine nuclei. The neurons of the basal plate form the motor nuclei of V, VI and VII.
Describe the development of the cerebellum
The cerebellum develops from the most posterior parts of the alar plates, above the level of the medulla. Cerebellar growths project over the top of the fourth ventricle and fuse in the midline, with migrating cells from the alar plates becoming the cerebellar cortex.
