CNS Development Flashcards
Lumen of the ______ forms the ventricular system of the brain
neural tube
The prosencephalon divides into the _____ and the ______
telencephalon, diencephalon
The ________ remains undivided during development of the CNS
mesencephalon
The rhombencephalon divides into the _____ and _______
metencephalon, myelencephalon
The ______ forms the cerebral hemisphere including the basal nuclei and internal capsule
telencephalon
The diencephalon forms the ______ and _______ as well as the _____ and _____
thalamus, hypothalamus, neural retina, optic nerve
The ______ forms the midbrain
mesencephalon
The metencephalon forms the ______ and _______
pons, cerebellum
The ______ forms the medulla oblongata
myelencephalon
initial flexures of CNS development are noticeable between weeks ______
4-5
initial flexures of CNS developement include the ______ between the ______ and ________; and the _______ between the ______ and ______.
cephalic flexure, prosencephalon, mesencephalon
cervical flexure, rhombencephalon, spinal cord
This initial flexure is not maintained in the adult:
cervical flexure (between the rhombencephalon and spinal cord)
3 primary vessicles are converted to 5 secondary vessicles by __________
deepening of all flexures
The deepening of the ______, _____, ______, and ______ flexures produces the 5 secondary vessicles
cephalic, cervical, pontine, telencephalic
At 8.5 weeks gestation, the ______ becomes C-shaped after rapid growth
telencephalon
The epithelium of the wall of the neural tube is ________
pseudostratified epithelium
The _____ is the innermost cell layer surrounding the lumen of the neural tube and is the site of ______
ventricular zone, cell division/proliferation
During the G1 —> S —> G2 phase of the cell cycle, progenitor cells in the ventricular zone have _____ morphology and attach to both the ______ and _____ surfaces.
fusiform (spindle-like, taper at both ends); ventricular surface, pial surface
During the ________ phase of the cell cycle, progenitor cell nuclei migrate to the pial surface and back to the ventricular surface
G1 —> S —> G2
During the M —> G1 phase of the cell cycle, progenitor cells _____________
lose contact with pial surface in mitosis, but daughter cells regain contact
asymmetrical division during mitotic proliferation of neuroepithelial progenitors produces ______
blast cells
50% of neuroblasts _______ during development
undergo apoptosis
The marginal zone is closest to the _______ surface
pial (basal) surface
asymmetrical division of neuroepithelial progenitors is ______ to the _____ surface of the ventricular zone
parallel, apical
_____ division produces neuroblasts which eventually migrate out of the ventricular zone to become glioblasts
asymmetric (radial)
Symmetrical division of neuroepithelial progenitors is _______ to the apical surface of the ventricular zone
perpendicular
The _____ forms immediately after the ventricular zone is formed
marginal zone
The ______ contains processes of proliferating cells within the ventricular zone
marginal zone
The _____ forms as post-mitotic neuroblasts migrate
intermediate zone
The _____ forms between the ventricular zone and marginal zone
intermediate zone
The ______ is located at the interface of the ventricular zone and the intermediate zone.
subventricular zone
The subventricular zone contains _________ and in some areas it also contains ______
progenitor cells of macroglia, stem cells
Cells that remain in the ventricular zone become _______ cells which line the ventricles in the brain
ependymal cells
Neuroblasts organized by location from the apical surface to the basal surface are as follows:
ependymal zone, ventricular zone, subventricular zone, intermediate zone, subplate, cortical plate, marginal zone
radial glial fibers extend from the _________ to the _______ to guide migrating neuroblasts
subventricular zone, cerebral cortex
Neuroblast migration always begins in the _______ and the first cells to migrate detach from radial glia close to the __________ and as time goes on successive waves of migrating neuroblasts detach closer to the ______
ventricular zone, ventricular surface, pial surface
Initial waves of neuroblast migration detach at the _______, later waves pass through layers of neuroblasts to detach close to the _____
intermediate zone/subplate, pial surface
Cerebral cortex forms from the expansion of the superficial part of the _______ into the _____ and ______
intermediate zone, subplate, cortical plate
The ______ is the future cortex lamina I
marginal zone
The cortical plate is the future _______
cortex laminae II-VI
The _______ and ______ become subcortical white mater, and the ______ is also a transient structure during development with transient synaptic connections
subplate, intermediate zone, subplate
The ventricular zone becomes the _______ layer
ependymal layer
Neuroblast migration begins at __ weeks and ends at __ weeks
6 weeks, 34 weeks
Initially neurons in layers ___ through ___ are undifferentiated functionally
II-VI
Layers ____ and ____ extend axons and are output layers.
III, V
Layer ___ receives thalamocortical axons and is an input layer
IV
The convolutions (reshaping) of the cortex are caused directly by ______
neuron migration
Formation of the ______ is complete by 16 weeks
primary sulci (lateral, longitudinal, calcarine)
______ is expressed at glial end feet and affects detachment of neurons from radial glia
Reelin (RLN)
Mutations in _______ disrupt the final stage of neuronal migration through the cortical plate
Reelin (RLN)
_____ is expressed in migrating neurons and interacts with microtubules
doublecortin (DCX)
Mutations in ______ result in arrest of neuron migration in subcortical white matter before reaching the cortical plate
doublecortin (DCX)
_____ is expressed in migrating neurons and interacts with dynein
lissencephaly (LIS1)
Mutations in _______ disrupt neuron migration and lamination
lissencephaly (LIS1)
A patient has thickened cortex with a cortical subplate but no cortical plate. His cortical layers are not deliniated. What mutation does he likely have?
Doublecortin (DCX) mutation
A patient has an inverted cortical plate and cortical subplate, what mutation does he likely have?
Reelin (RLN) mutant
A patient has a defect in development of his telencephalic flexure (which forms the lateral fissure) as shown on MRI. He also has continuity of the cortex from the surface of his brain into the channel of this defect. What disorder does he likely have?
schizencephaly
A patient dies and his autopsy reveals that a defect in the cerebral hemisphere left a cleft into his lateral ventricle. What disorder did he likely have?
schizencephaly
The 2 types of heterotopic disorders of cortical development are:
subcortical laminar (band) heterotopia, focal cortical dysplasia
A patient has a disorder of cortical development that causes his cortex to be excessively thick and lack lamination. The ventricles are enlarged on MRI. What disorder does he likely have and what mutation led to it?
subcortical laminar (band) heterotopia, DCX mutation (X-linked recessive)
Subcortical laminar (band) heterotopia is due to a ________ mutation which is _____ (type of mutation)
DCX mutation, X-linked recessive
A patient has a thick neural cortex and heterotopic aggregates of gray matter (periventricular) on MRI. What disorder of cortical development does he likely have?
focal cortical dysplasia
Subcortical laminar (band) heterotopia and focal cortical dysplasia are both caused by:
neuroblasts arrest in subcortical white matter before reaching the cortical plate
_______, a disorder of neuroblast migration, may be genetic or nongenetic
lissencephaly (genetic: LIS1 mutation; non-genetic: congenital infection with CMV as a fetus)
This disorder of neuroblast migration is characterized by smooth cerebral cortex and enlarged lateral ventricles:
lissencephaly
_______, a disorder of neuroblast migration, may be accompanied by microcephaly, dysmorphic facies, epilepsy, visual impairment, hypotonia, or intellectual disability
lissencephaly
Lissencephaly is often accompanied by ________, or ________, or ________
Dandy-Walker, Pachygyria (few wide gyri), polymicrogyria (multiple, excessively small gyri)
The _______ arises from the rhombic lip (alar plate structure that forms part of wall of 4th ventricle)
cerebellum
The _______ expand posteromedially to meet and fuse in the midline to form the cerebellar plate
rhombic lips (alar plate structure that forms part of the wall of 4th ventricle)
Fissures divide the ______ into flocculonodular lobes
cerebellar plate
The ___________ zone becomes the internal germinal (granular) layer of the mature cerebellar cortex, white matter, and cerebellar nuclei
intermediate zone (IZ)
Initially, the fetus has only these cortical layers in the CEREBELLUM:
ventricular zone and marginal zone
The ________ contains immature neuroblasts in the CEREBELLUM which are migrating outward (toward pial surface) along radial glia
intermediate zone/internal germinal layer
The immature migrating neuroblasts in the _______ zone of the CEREBELLUM become purkinje cells and golgi cells, others that do not migrate become cerebellar nuclei
intermediate zone
Cells that do not migrate in the __________ zone/_________ of the CEREBELLUM become cerebellar nuclei
intermediate zone/internal germinal layer
Neuroblasts in the _______ layer of the CEREBELLUM migrate inward (away from the pial surface) along radial glia
external germinal layer
The ______ of the CEREBELLUM is the 2nd layer of immature neuroblasts that forms at outer edge of the marginal zone
external germinal layer
The immature neuroblasts in the external germinal layer of the CEREBELLUM become _______ after they migrate
granule cells
neuroblasts in the external germinal layer of the CEREBELLUM that do not migrate become ______ cells and ______ cells
basket cells, stellate cells
The migrating cells of the ______ layer of the CEREBELLUM produce purkinje cells and golgi cells, while the non-migrating cells produce cerebellar nuclei
internal germinal layer
The migrating cells of the _________ layer of the CEREBELLUM produce granule cells
external germinal layer
The non-migrating cells of the _______ layer of the CEREBELLUM that stay near the pial surface are basket cells and stellate cells
external germinal layer
The ________ is the central area of the cerebellum on axial MRI
vermis
“molar tooth” sign in axial MRI is characteristic of _________ which is a disorder of cerebellar/hindbrain development
Joubert syndrome
The 4 disorders of cortical development are:
schizencephaly, subcortical laminar heterotopia, focal cortical dysplasia, lissencephaly
Clinical signs of _______ are hypotonia, truncal ataxia, developmental delay, oculomotor ataxia, episodic hyperpnea, and progressive worsening of this disorder
Joubert syndrome
__________ is characteristic of Joubert syndrome and is characterized by irregular, jerky eye movements secondary to role of the cerebellum in smooth pursuit eye movements
oculomotor ataxia
The only disorder of cerebellar development that is not genetic is:
Dandy-Walker malformation
This disorder of cerebellar/hindbrain development is characterized by hypoplasia of the cerebellar vermis and cystic dilation of the fourth ventricle
Dandy-Walker malformation
This disorder is characterized by a large cystic dilation of the fourth ventricle which looks like a large hypodense area in the posterior brain on both axial and sagital MRI
Dandy-Walker malformation
Clinical signs of ________ are hypotonia, delayed motor development and ataxia. Intellectual impairment in majority of patients)
Dandy-Walker malformation
________ is characterized by herniation of cerebellar tonsils through the foramen magnum
chiari malformation
Type II chiari malformation is associated with _________ diagnosed in this time in life: _______
meningomyelocele, childhood
Type I chiari malformation is associated with _________ and is diagnosed in this time in life: ______
being asymptomatic, adulthood
Syringomyelia is a hyperdense spot in the middle of the spinal cord near the cerebellum which is characteristic of _________
chiari malformations
All of the cells of the CNS develop from the neural tube except _______
microglia
macroglia derive from _________
mesenchymal cells
The 3 CNS neuron types are:
multipolar neurons in brain and spinal cord, LMNs, autonomic preganglionic neurons
The 3 types of CNS (macro)glial cells are:
astrocytes, oligodendrocytes, ependymal cells
______ is expressed at the apical cortical surface, while _____ is expressed at the basal (pial) surface
notch, numb
_______ amplifies level of stem cell population formed by perpendicular cleavage plane and symmetrical division
notch
_______ is associated with symmetrical neuronal and glial cell division
notch
Daughter neuronal or glial cell exposed to high numb closer to the basal surface undergoes _________ division and its cleavage plane is _______ to the basal surface
asymmetrical division, parallel
In early asymmetrical division, both Notch signaling and expression of bHLH biases neural progenitor cells towards becoming ________
neurons
Early asymmetrical division produces mostly ______, while later stages produce mostly ________
neuroblasts, glioblasts
Late asymmetrical division with Notch signaling but little expression of bHLH genes promotes _________ development
astrocyte
The _______ separates the (posterior) alar plate from the (anterior) basal plate
sulcus limitans
High BMP is present at the _______ and becomes the posterior horns in spinal cord
alar plate
High SHH is expressed in the ________ which becomes the anterior and lateral horns in the spinal cord
basal plate
The development of the basal plate is induced by the _______ through high levels of ______
notocord, SHH
The _______ in the brainstem divides alar and basal derivatives into lateral and medial columns
sulcus limitans
The lateral portion of the brainstem is derived from ________ and is called the _______ during development
neural crest, alar plate
The _______ of the developing brainstem is made up of afferent functional columns (VA, SA, cranial nerve nuclei)
alar plate
The _______ of the developing brainstem is made up of efferent functional columns (VE, SE, cranial nerve nuclei)
basal plate
The medial portion of the developing brainstem is made up of primarily ________
efferent functional columns (VE, SE, cranial nerve nuclei)
The ______ derivatives in the medulla are the gracile and cuneate nuclei, vestibular, and trigeminal, as well as the solitary nucleus and inferior olivary nuclei
alar plate
The _______ develop from the rhombic lip
inferior olivary nuclei
The dorsal motor nucleus of vagus, inferior salivatatory nucleus, hypoglossal, and nucleus ambiguus develop from the ________ of the medulla
basal plate
The ______ derivatives in the pons are the vestibular, cochlear, principle sensory, spinal trigeminal, solitary, and pontine nuclei
alar plate
The ________ develop from the rhombic lip
pontine nuclei
The _______ derivatives of the pons are the superior salivatory, abducens, facial, and trigeminal nuclei
basal plate
VA nuclei are more ________ in the pons and medulla than the SA nuclei
medial
Midbrain _______ derivatives include the superior and inferior colliculi, red nucleus, and substantia nigra
alar plate
Midbrain _______ derivatives include the EW, oculomotor, and trochlear nuclei
basal plate
immature neuroblasts (specialized neuroepithelial cells) that migrate through/to the intermediate zone are ______
apolar
The immature neuroblasts within the intermediate zone or at cortical plate extend ________
neurites
The longest neurite in a neuroblast is its:
axon
__________ and ________ contain dense actin filaments and their central core contains _______ and _________
lamellipodia, filopodia, tubulin, microtubules
central core of axon growth cones is made up of _______ and _______
tubulin, microtubules
The purpose of _______, ________ and ________ of growing axons is to explore and determine direction of growth of the axon
lamellipodia, filopodia, central core
Binding of ________ to __________ prevents axons of retinal ganglion cells of the temporal retina from crossing at the optic chiasm
EphB1, ephrin-B2
Radial glia at the cross point of the optic chiasm expresses ________ which prevents RGCs of temporal retina from crossing the chiasm
ephrin-B2
The _______ transpforms into a ________ as an axon reaches its target
growth cone, presynaptic nerve terminal
NGF, BDNF, and FGF are ___________
trophic factors secreted by a target cell to an axon that promote neuron survival
In neuromuscular synaptogenesis, a single site on a target cell is occupied by multiple axons, what stage of development are these axons in?
synaptogenesis
The first two steps in neuromuscular synaptogenesis are:
- growth cone approaches newly fused myotube
2. makes morphologically unspecified but functional contact
What type of synaptogenesis involves multiple axons converging on a single site on a target cell?
PNS neuromuscular junction
synapses in the CNS and the PNS are structurally dissimilar. True or false?
false
_____ provides a clinically useful measure of neurological maturation in the preterm infant
EEG
In _______ synaptogenesis, initial contact between an axon and a filopodium on a developing dendrite leads to a stable dendritic spine
CNS
CNS synaptogenesis involves a(n) ________ and a(n) __________ contacting each other
axon, filopodium of developing dendrite
_______ and ________ do not begin myelination until near term
optic nerve, geniculocalcarine tract
The _______ begins myelination at 4 months postnatally and continues into mid-adolescence
corpus callosum
The ________ reflects myelination of the corticospinal tract
Babinski sign
The _______ is normal in infants up to 18 months of age
babinski sign
