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What is the first event in the formation of the nervous system ?
Formation of neural plate
How does the first event in the formation of the nervous system occur?
thickening of epiblast layers cranial to the primitive pit; differentiates craniocaudally.
What structure releases inducing substances that diffuse to epiblast and what happens at the epiblast?
NOTOCHORD and the substances activate gene transcription – cells differentiate into a thick plate of columnar epithelial cells.
What types of molecules lead to induction of neural plate? and give 2 examlples?
Molecules that block the action of BMPs such as:
1. chordin
2. noggin
Give 3 other molecules that lead to induction of neural plate?
1. FGF'S
2. Wnt's
3. retinoic acid
What sets up the neural groove/midline?
Sonic hedgehog (SHH) from notochord
Rapid lengthening of the neural plate occurs concurrent with what?
somite development.
how do you form the neural canal?
E22, neural plate creases ventrally at midline, The lateral lips of the folds meet to form a tube – the neural canal.


Neural tube (canal) forms as the neural folds fuse in the midline and separate from the surface ectoderm.

1. Neural plate: a thickened plate of ectoderm along the dorsal midline of the early embryo that gives rise to the neural tube and crest.

2. Neural groove forms as the neural plate begins to fold inwards and it is flanked by neural folds, which are parallel and deepens as the neural folds begins to close over it.

3. Neural folds: they fuse in the midline to form the neural tube and they are the sites of neural crest cell differentiation.

4. Neural tube: forms as the neural folds fuse in the midline and separate from the surface ectoderm. lies btw the surface ectoderm and the notochord.
When does Formation of neural tube (Neurulation) begin?
It begins at day 22.
describe neurulation
Neurulation proceeds bilaterally from the occipital level and ends at day 26 with the closing of the cranial and caudal pores of the neural tube.
The neural tube develops from ?
Folds of specialized neuroectoderm.
The folding and formation of the tube is ‘induced’ by?
The mesodermal notochord.
Describe the neural tube closure?
It begins in the middle and zips-up toward rostral and caudal ends.
The neural tube develops into?
The Central Nervous System (CNS), that is, the spinal cord and brain.
Clumps of neural crest cells at the margin of the neural fold, remaining outside the tube form?
Adjacent somatosensory and autonomic ganglia and peripheral support cells.
The cranial part of the neural tube becomes?
The brain
The caudal part of the neural tube becomes?
The spinal cord
The cavity part of the neural tube becomes?
The central canal of the spinal cord and the ventricles of the brain
What is Secondary Neurulation?
Process resulting in the formation of the caudal spinal cord and filum terminale by the caudal eminence
This process generates neural tube to somite ?
somite 37.
Formation of caudal end of neural tube is completed by?
8 weeks.
What are Neural Crest Cells?
A transient migratory group of cells that emerge from the dorsal lip of the neural tube and give rise to a wide variety of structures throughout the body.
Neural crest cells that take superficial pathway, just beneath the ectoderm will form?
pigment cells of the skin
Neural crest cells that take the deep pathway via the somites will form ?
sensory ganglia, sympathetic ganglia, and parts of the adrenal gland.
5 ganglia that are Neural crest derivatives?
Dorsal root ganglia
enteric ganglia
chain ganglia
preaortic ganglia
cranial nerve ganglia (some)
What are other Neural crest derivatives?
1. Neural-like cells of the adrenal medulla

2. Schwann cells of PNS

3. The pia and arachnoid membrane of the brain and spinal cord.
The dura mater, is derived from? and it does what?
It is derived from mesoderm and it surrounds the neural tube structures
Roles of:
- Schwann cells
- Pia membrane
- Arachnoid membrane
- Subarachnoid space
- Schwann cells are support cells of the PNS that make myelin sheaths
- The pia follows every surface of spinal cord and brain and invests the surface of large penetrating arteries a short distance into the brain parenchyma.
- The arachnoid is attached to the pia by spidery-web processes (hence the name arachnoid)and it is a covering (meninges) of the brain and spinal cord.
- The subarachnoid space contains cerebrospinal fluid (CSF).
What is cytodifferentiation?
Process by which cells that will populate the nervous system are generated.
The 3 layers of the developing neural tube are?
1. Neuroepithelial (germinal epithelial) layer
2. Mantle layer
3. Marginal layer
What happens in the Neuroepithelial (germinal epithelial) layer of the developing neural tube?
This is the innermost layer and cell divison layer where:
A. neuroblasts form neurons
B. glioblasts form astrocytes and oligodendrocytes
C. it becomes the mononuclear layer of ependymal cells that line the central canal and future brain ventricles; source of adult stem cells.
What happens in the Mantle layer?
This is the middle layer and cell maturation layer where there is accumulation of neuron cell bodies - Gray matter
What happens in the Marginal layer ?
This is the outermost layer where axonal processes of local and distant neurons become ascending, descending and intersegmental tracts of the spinal cord - White Matter
What happens to the Mantle layer at the end of the 4th week?
At the end of the 4th week, the mantle layer becomes organised into the paired basal and alar columns of the ventral and dorsal quadrants of the spinal cord, respectively.
1. alar plate
2. basal plate
3. sulcus limitans
4. visceromotor neurons
1. alar plate is the somatosensory receiving area that is the future dorsal horn
2. basal plate is the somatomotor neuron area that is the future ventral horn
3. sulcus limitans is a crease of wall in the neural tube that divides the the alar and basal plates on one side.
4. visceromotor neurons are located in the basal plate closest to the sulcus limitans.
Describe development of
A. neural crest cells
B. motoneurons
A. There is a segmental Organization of neural crest cells that clump in relation to somite masses
B. Motoneurons extend axons towards somites to form ventral roots
What happens when there is outgrowth of ventral roots?
It triggers the extension of dorsal root ganglion axons into the dorsal horn (dorsal root)and towards the periphery
Describe Spina bifida?
It usually occurs in the sacrolumbar region and results from the failure of the neural tube to close.
Describe Spina bifida occulta?
It is a failure of the vertebral column to close and the only feature is hair growing where this occurs and it is the least severe type of spina bifida
Describe spina bifida meningocele?
It occurs when the arachnoid meninges protudes out forming a sac filled with CSF but the spinal cord is still in its normal position
Describe spina bifida meningomyelocele?
It occurs when the meninges and spinal cord project out and form a sac
Describe rachischsis?
In rachischsis, much of the spinal cord which is abnormal is open and covered by skin or meninges only and the neuronal material is defective as well.

A congenital abnormality (as spina bifida) characterized by a cleft of the vertebral column.
Describe Meningoencephalocele?
A protusion of both the meninges and brain tissue through a skull defect
Describe Anencephaly?
Failure of cephalic end of neural tube to close
so the brain fails to develop since no cranial vault is formed
What are the three primary brain vesicles?
1. Prosencephalon or forebrain
2. Mesencephalon or midbrain
3. Rhombencephalon or hindbrain
What 2 structures does the forebrain give rise to?
1. Telencephalon (endbrain)
2. Diencephalon (between-brain)
What 2 structures does the hindbrain give rise to?
1. Metencephalon (afterbrain)
2. Myelencephalon (medulla)
What are the five secondary brain vesicles?
1. Telencephalon (endbrain)
2. Diencephalon (between-brain)
3. Mesencephalon or midbrain
4. Metencephalon (afterbrain)
5. Myelencephalon (medulla)
What are 3 adult derivatives of the Telencephalon (endbrain)?
1. Olfactory lobes = smell
2. Hippocampus = memory
3. Cerebrum = intelligence

The lateral ventricle is the cavity for the telencephalon
What are 4 adult derivatives of the Diencephalon (between-brain)?
1. Retina = vision
2. Epithalamus = pineal gland
3. Thalamus= relay centers for
optic and auditory neurons
4. Hypothalamus = temperature,
sleep, and breathing

The third ventricle is the cavity in the diencephalon.
What is 1 adult derivative of the Mesencephalon or midbrain?
1. Midbrain = fiber tracts btw
anterior and posterior brain, optic lobes, and tectum


It contains a large cavity that will become the cerebral aqueduct.
What are 2 adult derivatives of the Metencephalon (afterbrain)?
1. Cerebellum = coordintion of
complex muscular movements.
2. Pons = Fiber tracts btw cere-
brum and cerebellum

Its cavity is the upper part of fourth ventricle.
What is 1 adult derivative of the Myelencephalon (medulla)?
1. Medulla oblongata = reflex center of involuntary actvities
Differentiate between the 3 flexures of the brain?
1. Cephalic flexure (midbrain
flexure):between the prosencephalon and rhombencephalon that folds prosencephalon ventrally

2. Pontine flexure: This is a dorsal flexure between the Metencephalon and myelencephalon
3. Cervical flexure, between the myelencephalon and spinal cord, that folds the brain ventrally relative to the spinal cord
What are the mature ventricular structures that arise from the primitive ventricles of:
1. TEL = lateral ventricles
2. DIE = Third ventricle (III)
3. MES = Cerebral aqueduct
4. MET = Fourth ventricle (IV)
(Upper part)
5. MYE = Fourth ventricle (IV)
(lower part)
Describe Hydrocephaly?
Results from the blockage of the cerebral aqueduct that normally drains cerebrospinal fluid from the lateral and third ventricles, therefore there is swelling in the rostral parts of the brain.
Describe Holoprosencephaly?
This is a craniofacial anomaly where there is lack of formation of the prosencephalon and the frontonasal, midfacial structures and the forebrain are deformed. It is due to teratogens such as alcohol, which inhibit induction of the prosencephalon during the 3rd week of development.
Describe what happens at the anterior neural ridge of the brain?
At the anterior end of the neural plate, the organizer of the anterior prosencephalon secretes Fgf8, which can impart anterior properties
What is Zona limitans intrathalamica (ZLI)?
It is in the middle of the diencephalon and it may lead to segmentation of the thalamus
What is Isthmic organizer (IsO)?
It is located at the junction of the midbrain and the hindbrain and it is important for the patterning of the mesencephalon and the cerebellum; Fgf8
How does the cerebellum develop?
-It is formed from a thickening in the rhombic lip of metencephelon at week 6. -By the end of the middle of the 3rd month, the swelling of the metencephalon, located over the 4th ventricle begins to form a bulge.
Development continues through birth.
Has 2 marginal zones
Describe the layering and zones of the cerebellum?
It has three layers:
1. molecular layer
2. purkinje cell layer
3. granular (internal)cell layer
It has 2 marginal zones
Describe dorsoventral Patterning and their inducers?
A. dorsal cell types are
induced by:
1. BMPs
2. nonneural ectoderm
3. roof plate
B. Ventral cell types are
induced by:
1. floor plate
2. Shh
Describe events of the roof plate of medulla oblongata
The roof plate stretched so much so that neurons from the alar plate are adjacent to neurons in the basal plate
-alar plate are sensory and
visceral afferents
-basal plate are motor: somatic and visceral efferents
Describe Radial and Tangential Cell Migration
-In the spinal cord, you have radial migration where the cells migrate upwards
-Tangential migration means the cells migrate far away
-The cerebral cortex is unique because it has a ventricular zone where cells migrate
Where are cerebral cortical neurons generated?
They are generated in the ventricular zone and migrate along radial glia, settling in an inside-out fashion and it is a six layered cortex.
What is unique about the development of cerebral cortex?
Sulcus and gyris help pack in more neuronal material since the cerebral cortex becomes more complex with development and it gives rise to all the neurons that populate the brain.
Differentiate between:
1. Callosal projection
2. Subcortical projection
3. Intracortical projection
1. Callosal projection:
Projects to areas of the

2. Subcortical projection: Projects to areas under the

3. Intracortical projection: Projects to areas within
the same lobe of the
cerebral cortex
What are the two theories that illustrate how growth cone sense molecular markers that guide axons to the correct route?
1. Contact guidance theory
2. Chemoaffinity theory
What are the 2 molecules involved in contact-mediated attraction/permissive?
1. IgCAMs
2. ECM molecules (laminin,
What are the 3 molecules involved in long-range attraction?
1. netrin
2. neurotrophins
3. slits
What are the 3 molecules involved in contact-mediated repulsion/inhibitory?
1. ephrins
2. transmembrane semaphorins
3. ECM molecules (tenascin,
What are the 3 molecules involved in long-range repulsion?
1. semaphorins
2. slits
3. netrin
Give 2 examples of commissural axons in the dorsal cord and how do they project their axons?
Two examples of commissural axons in the dorsal cord are:
1. Netrin
2. Dcc
They project their axons ventrally and when they cross the floor plate, they make a sharp turn on the contralateral side. Then they migrate rostrally toward higher centers of the CNS. This pattern is extremely precise for all commissural axons.
What is Agenesis of the Corpus Callosum (ACC)?
It is a birth defect in which the structure that connects the two hemispheres of the brain (the corpus callosum) is partially or completely absent.

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