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Flashcards in SDL-4 Neuroembryology Deck (76):

The nervous system is derived from a portion of which germ layer?



Describe the portion of the ectoderm from which the nervous system develops.

The NS is derived from a portion of the ectoderm which is an identifiable entity distinct from the rest of the ectoderm by the beginning of the 3rd week of gestation.

This "neuroectoderm" or "neuroepithelium" is initially a plate.


Describe the development of the neural plate.

It thickens and elevates bilaterally as folds bounding a groove (the "neural groove"). The neuroectodermal cells then separate from the adjacent ectoderm, and the latter fuses over the dorsal mid-line as the skin.


At the time of separation of neuroectoderm from adjacent (skin) ectoderm, the neuroectodermal cells have what two fates?

Either they:
1. Remain near the midline and fuse to form a tubular structure ("neural tube") -or-
2. Disperse and undergo remarkable migratory paths (the "neural crest")


Describe "primary neurulation"

The neural folds begin their fusion to form the neural tube on embryo day 20. This fusion progresses rostrocaudally and is completed by day 23.
The two major processes of primary neurulation are the fusion of the folds of neuroectoderm to form a tube, and the closure of the neuropores.


From the outset the neural tube contains a lumen called...?

The "neurocele"


As with any other tubular structure derived in this fashion, the ends of the neural tube remain open temporarily. In the case of the neural tube, its lumen initially communicates with __________, through openings called the _________ and ________ ___________.

Amniotic cavity;
Through the "anterior and posterior neuropores"


When does the anterior neuropore close?

Day 25


When does the posterior neuropore close?

Day 27


What is formed by primary neurulation (i.e. by fusion of neural folds to form neural tube, and closure of neuropores)?

The brain, brainstem, and C1-S1 spinal cord.


When does "secondary neurulation" start and finish?

Days 20-40


Describe "secondary neurulation".

A mesodermal cell mass located in the caudal aspect of the embryo (the "caudal eminence") differentiates into a "neural cord", cavitates, and secondarily attaches to the neural tube (which is formed by primary neurulation).


What is formed by secondary neurulation (i.e. by differentation of the mesodermal cell mass ("caudal eminence") in the caudal region into the "neural cord", and its attachment to the neural tube)?

The S2-Co1 spinal cord levels
(recall that C1-S1 are formed by primary neurulation).


What malformation can occur during secondary neurulation?

Spina bifida


Describe the problem that occurs with secondary neurulation that causes spina bifida.

The caudal eminence does not join properly with the neural tube.


The neural tube retains its lumen ("neurocele") which eventually differentiates into...?

The ventricular system within the brain
The central canal within the spinal cord


During the early stages the neurocele lumen is limited by a layer of cells called...?

The "neuroepithelial layer" (also called the proliferative or ventricular layer)


What cells develop from the neuroepithelial layer (the limiting cell layer of the neurocele lumen)?

The intrinsic cells of the CNS:
Neurons and macroglia (astrocytes and oligodendrocytes).


After completing its proliferative function the neuroepithelial cells differentiate into...?

Ependymal cells, which ultimately line the ventricular system and the central canal.


The neural and macroglial cells derived from the neuroepithelial layer migrate from this region and form the ______ layer.

Mantle layer (neural and macroglial cells).
(Later: gray matter)


The mantle layer (neural and macroglial cells) is surrounded initially by nerve fibers arising from cells in the mantle layer, and this outer layer is called the ________ layer.

Marginal layer (nerve fibers of neural and macroglial cells in the mantle layer).
(Later: white matter)


Thus, the very early neural tube is characterized by what three layers?

Proliferative, mantle, and marginal.


The mantle layer in early stages of neural tube development is not uniform in shape, but shows dorsal and ventral thickenings, called...?

Alar (dorsal) and basal (ventral) plates.


Alar plate (location, function?)

Dorsal, sensory


Basal plate (location, function?)

Ventral, motor


What is the sulcus limitans?

A groove, located along the wall of the neurocele, that demarcates the alar from basal plates.


True/False: The roof and floor plates lack neuronal cell bodies.

True. At some sites they contain axons crossing from one site to another and at other sites they consist of cells of the proliferative layer juxtaposed to the developing pia mater.


In the process of differentiation of the rostral portion of the neural tube, what are the initial three primary vesicles that form?

1. Prosencephalon (forebrain)
2. Mesencephalon (midbrain)
3. Rhombencephalon (hindbrain)


What does it means to say that the prosencephalon (forebrain) is "supratentorial"?

It is that portion of the brain in the anterior and middle cranial fossae.


What does it mean to say that the mesencephalon (midbrain) and the rhombencephalon (hindbrain) are "infratentorial"?

They are the portions of the brain in the posterior cranial fossa.


As the walls become more complex, the three primary vesicles are further subdivided into what 5 secondary vesicles?

1. Telencephalon ("end brain") - cerebral hemispheres
2. Diencephalon ("tween" brain) - diencephalon
3. Mesencephalon (mid brain)
4. Metencephalon ("after brain") - pons and cerebellum
5. Myelencephalon ("marrow brain") - medulla.

*Note that prosencephalon (forebrain) forms the telencephalon and diencephalon; the mesencephalon (mid brain) stays put; and the rhombencephalon (hind brain) forms the metencephalon (pons and cerebellum) and myelencephalon (medulla).


Within the brain, the lumen of the neural tube (neurocele) persists as...?

The ventricular system


What develops within the cavity of the ventricular system?

The "choroid plexus"


What is produced within the cavities of the ventricular system by the choroid plexus?

Cerebrospinal fluid


CSF flows through the cavities in the ventricular system (which have choroid plexus) and passes into...?

Subarachnoid space


The CSF flows from the ventricles into the subarachnoid space through openings associated with the 4th ventricle, which is the derivative of the lumen of which brain vesicle?

Rhombencephalon (hindbrain)


The lumen of the neurocele associated with the future spinal cord remains as...?

The central canal


In areas not occupied by the choroid plexus, the lumen (neurocele) is lined primarily by...?

Ependyma - which differentiates from the neuroepithelial (proliferative) layer.


With the development of the cortical areas (cerebral cortex, cerebellar cortex), the cellular arrangement of the walls is modified so that the ______ matter occupies the superficial aspects, whereas the ______ matter forms an inner core. (**This is the phenomenon of CELLULAR MIGRATION)

Gray matter: superficial
White matter: Inner core


What cells serve as guides in the complex cellular migration?

Radial glial cells


After playing out their guidance roles, what do radial glial cells differentiate into?



What is the important phase of neuronal development that occurs once generation and migration are complete?



Describe the differentiation of neural cells.

The elaboration of processes and the establishment of synaptic contacts. Also, the formation of myelin by oligodendrocytes on their axons.


How much mesoderm or mesenchyme is in the CNS?

Very little. Mostly the brain and spinal cord are masses of neuroepithelial or neuroectodermal cells. The little mesoderm or mesenchyme is represented by a secondary invasion of the blood vessels and a group of cells called the microglia. The microglia are involved in inflammatory processes in phagocytosis and in immune responses within the CNS.


The cells of the neural tube stay within that structure and give rise to relatively few cell types (neurons, astrocytes, oligodendrocytes, ependyma). The cells of the neural crest, however, migrate from their site of origin soon after separating from the remainder of the neuroepithelium and differentiate into what (many) cell types?

1. Some remain near the neural tube and contribute to the leptomeninges (arachnoid and pia mater) and to the sensory ganglia of both cranial and spinal nerves (the primary sensory neurons and their associated satellite cells).
2. Autonomic motor neurons and associated satellite cells of the autonomic ganglia. Thus, the trunk or chain ganglia and the prevertebral (preaortic) ganglia of the SNS, and the terminal ganglia of the PSNS.
3. Adrenal medulla; chromaffin cells (posterior body wall)
4. Melanocytes (skin)
5. Schwann cells (the myelinating cells of peripheral (spinal and cranial) nerves).


Waardenburg syndrome

An inherited disorder characterized by hearing loss and abnormal pigmentation, caused by abnormal neural crest cell migration.
Often have two different eye colors, and a patch of white hair at a very young age.


Major subdivisions of the neural tube (neuromeres) are under the control of what genes?

Hox genes (homeobox genes)


How do the Hox genes function?

They establish boundaries between different segments of the neural tube and direct the formation of cranial nerves and their branchial arches.


Induction into the dorsal-ventral patterns is under the influence of...?

DORSAL: Bone morphogenic proteins (BMPs)
VENTRAL: Sonic hedgehog protein (SHH)


What is the function of "neurotrophins"?

Necessary for the survival of the neuron once it has sent its axon to the appropriate target.


How do neurotrophins function?

By preventing programmed cell death (apoptosis), and also by causing the survival of a subset of an original, much larger, population of neurons.


What are some examples of neurotrophins?

Nerve growth factor (NGF) - first one discovered, neural crest cell survival depends on NGF. e.g. Excess NGF leads to survival of many more DRG neurons, and hyper-innervation of the skin (or vice versa)
Brain-derived neurotrophic factor (BDNF)
Ciliary neurotrophic factor (CNTF)


Disorders of primary neurulation ("neural tube defects) include...?

Craniorachischisis totalis
Arnold-Chiari malformation


Craniorachischisis totalis

The total failure of neurulation. The neural plate lateral edges never fuse. There is no brain or spinal cord.



A defect in anterior neuropore closure. The initial point of fusion to the posterior neuropore is normal while no fusion occurs rostral to the brainstem. There are no cerebral hemispheres. The insult occurs prior to 24 days gestation. Some infants are liveborn but succumb early.



A failure of posterior neuropore closure. The neural plate caudal to the neck is open with no bony or skin covering. Onset by 24 days gestation. All are stillborn.



An outpouching of neural tissue which results when anterior neural tube closure occurs only partially. Usually occipital. Occurs by day 25. Maternal hyperthermia between day 20-25 may be a cause. Both fevers and saunas and/or hot tubs are culprits.



Partial failure of posterior neural tube closure. Most occur over the lumbar area (last region to close). Exposed neural elements are not covered by bone and may or may not be covered by a sac of skin. Occurs by day 27. Incidence up to 5/1000 live births. Hydrocephalus occurs in most. Associated problems vary with level of defect but include loss of sensory and motor function, sphincter dysfunction, rapidly enlarging head circumference.


Arnold-Chiari malformation

Hydrocephalus associated with myelomeningocele. Various degrees, may consist of inferior displacement of posterior fossa structures and bony defects in the foramen magnum and upper cervical vertebra.


How is myelomeningocele diagnosed prenatally?

Based on ALPHA-FETOPROTEIN levels. With open neural tube defects, this protein is found in increased amounts in maternal serum and amniotic fluid.


What reduces the risk of neural tube defects?

Multivitamin supplementation, especially the use of FOLATE, during pregnancy


Disorders of secondary neurulation (i.e. defects of CAUDAL neural tube formation) are distinguished by...?

Closed skin over the lesion as well as by the caudal location.


Why are defects of secondary neurulation called OCCULT dysraphic states?

Because they may escape detection for some time.



Split spinal cord


A dermal sinus

A tract usually from a dimple, may be a cause of CNS infection


Tethered cord

The caudal end of the cord is fixed by fibrous bands. Fat pads (LIPOMAS) are frequently associated with these lesions.


Caudal regression syndrome

Occurs with increased frequency in infants of diabetic mothers:
Results in sacral hypoplasia and hypoplastic femurs.


Ventral induction refers to events under the influence of prechordal mesoderm. This occurs in weeks 5-6 of gestation at the ventral side of the rostral end of the embryo, forming the face and forebrain.

What is the major disorder associated with ventral induction?



What is holoprosencephaly?

Failure of cleavage of the forebrain (telencephalon and diencephalon) into paired hemispheres.
The face may appear unusual with a single eye (cyclopia) and a single nostril (cebocephaly).
Caused by chromosomal disorders, diabetic mothers and genetic syndromes.


Disorders of neuronal proliferation include macrencephaly (large brain) and microcephaly (small brain) and is influenced by genetics, irradiation, alcohol, and intrauterine infection.

When does macrencephaly/microcephaly occur?

By 2-4 months gestation


Disorders of migration include disordered gyral development. When do disorders of migration occur?

By the 3-5 month of gestation



Cleft brain, sometimes bilaterally. If the defect is small, and does not extend long distances along the dorsoventral axis, then the term "porencephaly" can be used.



Smooth brain with few or no gyri



A brain with broad, fewer than usual gyri
(Pachyderm=thick skin)


Polymicrogyri (polygyri)

A brain that has regions with too many small gyri. Histology may revels that many more additional gyri are present than can be detected grossly.



The least severe of migration defects, referring to normal islands of tissue deposited in the wrong place.