Embryological Development of The Spinal Cord Flashcards
what is a morula?
what is formed after this stage?
Morula: solid ball of cells
Morula is rearranged to form the Blastula
Blastula: fluid filled sphere with cells forming the outer surface
This occurs at embryonic day 6
what is gastrulation?
when does it take place?
Gastrulation is the most critical stage of development of individuals
During gastrulation the various cell types of the blastula move around to take up positions that they will occupy in the fully developed individual
The resulting embryo after gastrulation is known as the Gastrula
At embryonic stage of Day 16, the Gastrula becomes trilaminar in profile
define trilaminar in relation to embryology
In triploblastic organisms, the gastrula is trilaminar - composed of three germ layers
The germ layers are referred to as (from outside to within)
Ectoderm
Mesoderm
Endoderm
what is the structure of the three germ layers of the embryo and what do they form?
All the tissue within humans are derived from these three primary layers of the embryo:
The outside layer is the ectoderm
forms the skin and neural tissue
the middle layer is the mesoderm
forms the skeleton and cardiac tissue
inner layer is the endoderm
forms the digestion and respiration viscera
what layer does neural tissue arise from?
The skin and neural tissue arise from a single layer, known as the ectoderm
This occurs as a response to signals produced by a structure called the notochord (a structure of the mesoderm)
The part of the ectoderm that receives the signals are destined to be nervous system tissue.
The part of the ectoderm that does not receive signals from the notochord will develops to become skin.
what is Notogenesis?
explain the process
Notogenesis: the development of the notochord
The notochord is the defining structure forming in all chordate embryos
At the end of the gastrulation phase, the notochord (mesoderm) is laid down ventral to the ectoderm.
As a result of ‘notogenesis’ the embryo changes from a circular organisation to an axial (flat) one.
The notochord sends out a signal to the ectoderm.
The part of the ectoderm that does not receive signals form the notochord will develops to become skin.
This causes some of these cells to form the first structure from which the nervous system originates => The neural plate
This is the start neurulation - the development of the human nervous system
The embryo at this stage is termed the neurula
In the next step of neurulation, the edges of the neural plate begin to fold inward, forming the neural groove.
The neural plate then closes at the neural plate border - to form the neural tube, from which the entire brain and spinal cord will develop
The neural tube has a slit in the centre. The central canal of the spinal cord and ventricular system of the brain develop from this slit.
during neurulation, how is the neural crest formed?
what does the neural crest develop into?
The neural plate border during neurulation, is exposed to a unique combination of factors from the adjacent skin, underlying mesoderm, and from the rest of the neural plate.
As a result, they are induced to form neural crest.
The neural crest cells downregulate cadherin expression (type of cell adhesion molecule) and delaminate.
They transform from epithelial cells into migratory mesenchymal cells and then migrate along defined pathways either side of neural tube to form structures.
The migrating neural crest cells will develop in some of the following structures:
- Smooth muscle and connective tissue
- Peripheral nervous system neurones and Glia
- Endocrine and para-endocrine cells
- chromaffin cells of adrenal medulla
- Skin & bones of face & neck
- melanocytes
- Ganglia
There are two migratory streams for neural crest cells.
what 3 streams do the neural crest cells take when developing?
depending on where the neural crest cells are found, it will determine cell fate
Trunk Neural crest cells (level of the sixth somite to the most caudal
somites) migrate and develop into:
1) sympathoadrenal> sympathetic ganglia and adrenal gland
2) Dorsal root ganglia> sensory neurons
3) Melanocytes
Lumbosacral neural crest cells: parasympathetic neurons and enteric nervous system
Cranial neural crest cells: sensory CN nuclei, parasympathetic ganglia, facial skeleton
Sympathetic from trunk NC cells!
Parasympathetic from lumbosacral, cranial, vagal and circumpharyngeal neural crests!
what is the first migratory stream for neural crest cells? (sensory lineage)
what 2 directions do sensory neurones extend to?
Neural crest cells migrate along ventrolateral stream and stop just medial to somites
They aggregate to form dorsal root ganglia and separate into 2 general lineages:
- Sensory neurons
- Glial cells (Schwann cells and satellite cells)
Sensory neurons extend processes in two directions: dorsomedially to the neural tube and ventrolaterally into the growing spinal nerve
This has partly been established by outgrowth of motor neuron axons from the basal plate.
Sensory neurons send axons into dorsal horn.
Motor neurons send axons out of ventral horn
essentially how the DRG forms
what is the second migratory stream for neural crest cells? (sympathoadrenal lineage)
Neural crest cells also migrate along the ventral stream
This is dependent on the expression of Phox-2 and Mash-1
Bone morphogenic proteins (BMPs) from the aorta help specify the bi-potential progenitors:
Sympathetic ganglion neurons: induced by presence of FGF and NGF (fibroblast & nerve GFs)
Adrenal chromaffin cells: induced by glucocorticoids in adrenal gland
Some also become part of prevertebral ganglia
explain the steps in formation of the neural tube
Formation of nervous system occurs during the embryonic stage: End of second week to end of eighth week
Folding and closure of the neural tube occurs first in the cervical region
The neural tube then “zips” up toward the head and toward the tail, leaving two openings which are the anterior and posterior neuropores
The anterior pore forms the cranial pore.
The posterior pore develops into the spinal pore.
The anterior neuropore closes around day 25 allowing the brain to develop.
If anterior neuropore does not close the brain will not develop.
The posterior neuropore closes around day 28
This ends neurulation
If the neural tube does not close properly it will result in spina bifida
what are the 3 brain vesicles that form?
As the embryo develops the anterior (rostral) part of the neural tube forms three primary brain vesicles - the tripartite brain
Prosencephalon (forebrain)
Mesencephalon (midbrain)
Rhombencephalon (hindbrain)
Tripartite brain begins to assume curved crescent shape due to the formation of cephalic flexure at the level of mesencephalon & cervical flexure between rhombencephalon & spinal cord
what does further differentiation of the tripartite result in?
Further differentiation of the Tripartite results in the Pentapartite brain (3 swellings to 5 swellings)
Structures of tripartite brain develop into a more mature brain
1. Prosencephalon develops into the…
telencephalon which then develops into the cerebrum
diencephalon which then develops into the thalamus & hypothalamus
2. Mesencephalon - develops into the midbrain
3. Rhombencephalon develops into the…
Metencephalon which then develops into the cerebellum and pons
Myelencephalon which then develops into the medulla oblongata
the developing neural tube is divided into 4 plates.. what are they?
Roof plate: a signalling centre, influences differentiation of cells in the Alar plate
The dorsal median septum is what is left over from the roof plate
Alar plate: gives rise to the dorsal horn of the spinal cord
Basal plate: gives rise to the ventral horn of the spinal cord
Floor plate: a signalling centre, influences differentiation of cells in the Basal plate
the ventral fissure is what is left over from the floor plate
the sulcus limitans is the sulcus in the middle (opening)
how does early signalling establish the neural crest, alar plate, and basal plate?
After neural tube closure, BMPs from skin induce expression of BMPs in the roof plate which largely cause development of the alar plate
Shh from the notochord induces expression of Shh in floor plate, which largely causes development of the basal plate giving rise to motor neurones
The neural crest is located in the intermediate zone between Shh from the notochord and BMPs from the skin
how is grey and white matter formed?
once the neural tube has formed, the cells that are found within are known as the neuroepithelia.
from the 4th somite onwards..
anything caudally forms SC
anything rostrally forms the brain
neuroblasts (neuronal pre-courser cells) are produced in the intermediate zone
as neurones develop they tend to start off in the ventricular zone then migrate towards the marginal zone
neurones from the intermediate zone go on to form grey matter
neurones from the marginal zone go on to form white matter (axons and glial cells)
what are neural tube defects?
what are the risk factors of NTD?
Neural tube defects (NTDs)- failure of the neural tube to close, results in:
* cranial defects
* spinal dysraphism
Open NTDs occur in about 0.1% of live births
Can be detected by antenatal Ultrasound and or screening
Risk factors: Mothers age (older and younger
mothers)
Folic acid deficiency
Maternal diabetes/ obesity
what is the most severe type of NTD?
what is failure of the cranial neuropore to fuse called?
what is failure of the caudal neuropore to fuse called?
Rachischisis- most severe, complete inability to close
Failure of the cranial neuropore to fuse:
Anencephaly
Cranial bifida/ cranial meningocele
Failure of the caudal neuropore to fuse:
spina bifida
* Spina bifida occulta
* Spina bifida cystica
* Meningocele- Spinal cord not involved
* Myelomeningocele- Spinal cord involved
what is anencephaly?
NTD towards the cranial part of the body
lack of cranial structures being formed
cranial bifida- a cyst forms in regions known as fontanelles (that are very soft)
there are a few types:
encephaloceale - parts of the brain in the cyst
Meningocele - meninges and CSF in the cyst
meningohydroencephalocele - herniation of meninges, CSF, brain parenchyma
what is spina bifida cystica?
2 different forms of spina bifida cystica:
Menigocele- Spinal cord not involved - therefore not as severe
Myelomeningocele- (more severe) herniating meninges
and neural tissue (most common form of
spina bifida cystica):
* co presents with Arnold- Chiari type 2
malformation and hydrocephalus
* motor and sensory impairments to lower
limb, bowels and bladder
what is spina bifida occulta?
Spina bifida occulta –hidden
* 2% population
* May not be diagnosed until adulthood
* failure of vertebral arches to fuse
* may be associated with a cyst
* Site may have overlying tuft of hair
summarise the embryological development of the spinal cord
Neurulation occurs in week 3-4.
* Day 17: Gastrulation results in the formation of trilaminar disc with a notochord structure in the axial mesoderm
* Day 19: Notochord signals to above ectoderm to thicken into neural plate and start to fold into a neural tube
* Neural tube starts to fuse fuses at cervical region (day 21) and starts to travel cranial and caudal to fully fuse
* Cranial neuropore first then caudal neuropore by day 28
* Incomplete closure leads to NTDs
* Notochord, overlying ectoderm (future skin) and paraxial mesoderm control the patterning of the neural tube
* Neural crest cells migrate and important in PNS: sensory ganglia, glia and autonomic nervous system formation
