Neuroscience 1a – Development of the Nervous System
Anil Chopra
- Review the development of the neural tube from the neurectoderm, and give an example of a clinical condition which results from abnormal development.
- Explain what is meant by the neural crest cells, and give examples of their developmental fates.
- Briefly describe how a simple tubular structure (the early neural tube) can give rise to the shape of the mature brain through differential growth and flexures.
- Outline the cellular basis of formation of the ependymal, grey matter (mantle layer) and white matter (marginal layer) regions of the spinal cord, and the separation of the grey matter into sensory (alar) and motor (basal) regions.
- Briefly outline how the development of the brainstem diverges from that of the spinal cord.
- Briefly outline how cortical layers form from the neuroepithelium.
Early Development
A)Trilaminar stage – 3 layers
- Ectoderm thickens up in midline and becomes neural plate
- These fold to become neural folds
- Fuse to become neural tube.CNS
B)Neural Crest PNS
- Separates off and moves laterally.
Neuroepithelium of Neural Tube
- forms the cells of the CNS
Neuroblasts
- Develop into neurones with cell bodies in the CNS.
Glioblast
- Give rise to glial cells (astrocytes, oligodendrocytes)
- NB. Microglia develop from the mesoderm as they are blood cells that develop
Ependymal Cells
- Single layers of lining cells
Neural Crest Cells
- cells found at the tips of the ridges of the neural groove and are isolated in neurulation. They migrate during development to form:
Sensory neurones of dorsal root ganglia and cranial ganglia
Postganglionic autonomic neurones (e.g. sympathetic chain).
Schwann cells of Peripheral Nervous system.
Non-neuronal derivatives e.g. melanocytes
Cellular Process
Proliferation occurs at the walls of the neural tube. This involves several repeats of the cell cycle.
Differentiation occurs on the outer surface of the CNS. They become neuroblasts and glial cells.
The neural tube surrounds the neural canal which in turn forms the canal of the fully developed spinal cord
Neuroblasts are contained within the tube
The neuroblasts adjacent to the canal in the Ependymal layer divide and migrate outwards within the tube forming the mantle layer, where they differentiate into neurones and form the grey mater of the cord
These cells then send fibres/developing processes out peripherally forming the white layer of the cord = marginal layer
The neuroblasts in the primitive grey matter form 2 discrete populations – the alar and basal plates separated by a shallow groove called the sulcus limitans
- Alar Plate – forms the posterior dorsal sensory horns of the cord
- Basal Plate – forms the anterior ventral motor horns of the cord. It also forms the parasympathetic and sympathetic pre-ganglionic neurons
In the first 8 weeks the spinal cord and vertebral column are the same length. After week 8 the vertebral column grows faster, so by week 40 the spinal cord stops at L3, and by adult life L1
The spinal cord is clothed in 3 layers of meninges similar to the brain, but with certain differences:
There is an extradural (epidural) space containing fat and a venous plexus
The pia mater has lateral projections called dentate ligaments which extend to the dura and help to stabilize the spinal cord
The lower end of the spinal cord is anchored to the coccygeal vertebrae by a strand pia mater (pial thread) called the filum terminale
The subarachnoid space below the end of the spinal cord, the lumbar cistern (L1), contains the lumbar & sacral spinal roots (nerve roots) is called the cauda equine
The strand of the pia mater between the coccyx and lower end of the spinal cord = fibrum terminale.
Neural Tube formation
First signs of nervous system development occur in the third week of gestation
Initial development is under the influence of secreted factors from the notochord with the formation of the neural plate along the dorsal aspect of the embryo
Fusion of neural groove to form the neural tube starts half-way along at the level of the fourth somite and continues caudally and rostrally, with closure by 4th week of gestation
Rostral (head) end fused on day 25
Caudal (tail) end fused on day 27
Folding = neurulation
Ectoderm of trilaminar disc → neural plate → folds to form neural groove → neuroepithelium of neural tube and neural crest cells
Abnormalities in process of closure:
Ancephaly – at the anterior/rostral end → no cerebral vesicles form and so no brain development
Spina Bifida – at the posterior/caudal end → leads to defects in meninges and neural tissue → herniation
Development of the Spinal Cord
After more proliferation occurs…
Spinal Cord Roots
Spinal cord lies within the vertebral canal and extends from the foramen magnum to the lower border of L1
It is enlarged in two sites – cervical and lumbar regions, corresponding to innervations of the upper and lower limbs
It consists of a core of grey matter surrounded by white matter. The neuronal cell bodies which make up the central grey mater are arranged in laminae (of Rexed). The white matter comprises myelinated and non-myelinated axons with short pathways that interconnect adjacent segments of the spinal cord and longer tracts to and from the brain
The posterior dorsal horns receive sensory input via spinal nerves and their accompanying cell bodies in the dorsal root ganglia. This information is used in spinal reflexes or is projected to the brain
Motor and pre-ganglionic autonomic fibres exit via the anterior ventral root. The motor cell bodies are found in the ventral horn of the spinal cord while the pre-ganglionic cell bodies of the nervous system are found in the intermedio-lateral column of the spinal cord
In the thoracic and upper lumbar regions the intermediate horns contain sympathetic pre-ganglionic motorneurons whose axons control visceral function via the ventral roots and spinal nerves forming the intermediolateral column
Development of The Brain
The brain develops from the top (rostral) of the neural tube.
In the first 3 weeks it enlarges and forms, 3 Primary Vesicles
Future forebrain
Future midbrain
Future hindbrain
During the next week it develops into 5 vesicles
- Hind brain splits into 2 (pons & medulla).
- Forebrain splits into 2 separate parts (becomes the 2 cerebral hemispheres)
At 8 weeks
- Lateral ventricles form in forebrain
- Third ventricle in the middle
- Cerebellum outpouch from hindbrain.
At 4 weeks, 2 flexures fold the neural tube inwards.
At 8 weeks, folding becomes more and more exaggerated.
Folding of the tube creates 3 flexures:
Cephalic flexure – between 1st and 2nd vesicles
Pontine flexure – between 2nd and 3rd vesicles
Cervical Flexure – between 3rd vesicles and spinal cord
Development of the Brainstem
The arrangement of the brainstem is similar to that of the spinal cord. Exceptions to note are:
- Neurones are clustered together into nuclei.
- Fourth ventricle runs in the middle, disrupting the pattern of grey matter.
- Neurones with motor function lie medial and ventral.
- Neurones with sensory function lie lateral and dorsal
- Nuclei with autonomic functions lie in between these.
Development of the Cortex
Cortex of the cerebral hemispheres and cerebellum is formed from the migration of neuroblasts formed from the neuroepithelium toward the surface of the pia. This pattern is different for the different structures.
Developmental Disorders of the NS.
- All the development has to occur at the right time.
- It is controlled by a mixture of genetic programming and the environment.
- It occurs early in gestation.
- It involves various different complicated processes including proliferation, differentiation, migrastion, synapse formation.
- Genetic mutation and environmental factors such as dietary insufficiencies and teratogens may interfere with the processes.
Research: - replace lost neurones by regulation of stem cell differentiation
- axon guidance can be used in inducing CNS regeneration.