Embryology Flashcards
Which one of the following correctly describes the order of embryological stages of CNS development?
a. Blastogenesis, gastrulation, dorsal induction, ventral induction, neural proliferation, neuronalmigration, and axonal myelination
b. Dorsal induction, ventral induction, gas-
trulation, neural proliferation, neuronal
migration, and axonal myelination
c. Gastrulation ventral induction, dorsal
induction, neural proliferation, neuronal
migration, and axonal myelination
d. Neural proliferation, gastrulation dorsal
induction, ventral induction, neuronal
migration, and axonal myelination
e. Ventral induction, gastrulation, dorsal
induction, neural proliferation, axonal
myelination, and neuronal migration
a. Blastogenesis, gastrulation, dorsal induction, ventral induction, neural proliferation, neuronalmigration, and axonal myelination
Below is a simplified timeline of neural develop- ment. It is worth noting that different brain regions have a unique course of ontogeny. Late
developing structures, including the cortex, hip- pocampus and the cerebellum set the stage for differential periods of vulnerability to insults in a regionally specific manner. Timings for individ- ual events vary between sources for events beyond ventral induction, but the general sequence is as follows:
Which one of the following statements
regarding gastrulation is most accurate?
a. It is the process by which the bilaminar
disc is converted into a trilaminar disc
b. It can result in lipomyelomeningocele if
disturbed
c. It is not dependent on bone morphoge-
netic protein expression
d. It starts with closure of the cranial
neuropore
e. It occurs from embryonic days 10-12
a. It is the process by which the bilaminar
disc is converted into a trilaminar disc
Gastrulation occurs between D14 and D17, and is the process by which the bilaminar disc (consisting of epiblast facing the amniotic cavity and the hypo- blast facing the yolk sac) becomes a trilaminar disc with formation of an intervening third layer, the mesoblast (future mesoderm). On day 14 or 15 a strip of thickened epiblast/ectoderm (primitive streak) appears caudally in the midline of the dorsal surface of the embryo to define the craniocaudal axis. The cranial end of the primitive streak forms the primitive (Hendersen’s) node, and shows a cen- tral depression called the primitive pit. Ectodermal cells start migrating towards the primitive streak, pass inward at the primitive pit to the interface of ectoderm and endoderm, and then migrate laterally to form the mesoderm. The two paired notochordal anlagen (primordia) then fuse in the midline to form a single notochordal process (“notochordal integra- tion”; D16). The primitive node defines the cranio- caudal axis, the right and left sides and the dorsal and ventral surfaces of the embryo. Prospective noto- chordal cells in the wrong craniocaudal position undergo apoptosis maintaining segmental noto- chordal formation. Multiple signaling molecules, such as bone morphogenetic protein (BMP), fibro- blast growth factor (FGF), and Wnt are essential for gastrulation to occur. BMP is very important in establishing the rostrocaudal polarity. In addition, multiple factors and genes are implicated in pattern- ing the primitive body axis (e.g., brachyury, sonic hedgehog (SHH), and HNF-beta genes). Defects in gastrulation (integration or segmental formation) affect development and differentiation of all three primary cell layers and cause abnormalities from the occiput downwards, e.g., split cord malforma- tion (diastematomyelia and diplomyelia), neuren- teric, dermoid, and epidermoid cysts, anterior and posterior spina bifida, intestinal malformation, duplication and fistula formation, and anterior meningocele.
Which one of the following statements about
primary neurulation is most accurate?
a. Anterior neuropore closure approxi-
mately occurs on D19
b. Disjunction results in formation of the spi-
nal canal below the posterior neuropore
c. Fusion of the neural folds starts at the
anterior neuropore and proceeds caudally
in a zip-like fashion until it reaches the
posterior neuropore
d. Notochord induces the overlying ectoderm to differentiate into a flat area of specialized neuroectoderm called the neural plate
e. SHH/morphogen secretion on D14
causes the neural plate to form median
hinge points and start invaginating along
its central axis to form a neural groove
(with neural folds on either side)
d. Notochord induces the overlying ectoderm to differentiate into a flat area of specialized neuroectoderm called the neural plate
Dorsal induction (3rd-4th weeks; D17-D28) includes primary neurulation, secondary neurula- tion and formation of the “true” notochord. Pri- mary neurulation involves separation of neuroectoderm in the neural plate from cutane- ous ectoderm to form the neural tube (brain and spinal cord) as far caudal as S2/3. The steps are summarized below:
* Neuralinductionandformationoftheneu- ral plate: the notochord induces the overly- ing ectoderm to differentiate into a flat area
of specialized neuroectoderm (neural plate). Relative to Hensen’s node, the neu- ral plate expands cranially and narrows/ elongates the parts on either side of the pri- mary streak—these areas will form the brain and spinal cord, respectively. This process is regulated by multiple genes, including brachyury and Wnt.
* SHH/morphogen secretion on D18 causes the neural plate to form median hinge points and start invaginating along its cen- tral axis to form a neural groove (with neu- ral folds on either side).
* These folds progressively increase in size and flex to approach each other, until they eventually fuse in the midline to form the neural tube (regulated by PAX3 genes). Fusion occurs in a zip-like fashion, proba- bly at multiple sites but first at the level of the 4th somite (future craniocervical junction).
* The cranial end of the neural tube (anterior neuropore) closes first at the site of the lam- ina terminalis on D24-26, followed by the posterior neuropore on D26-28 to com- plete primary neurulation. Note that the posterior neural pore is not located at the caudal tip of the neural tube. The caudal part of the spinal cord and the lowest sacrum portion is formed from the solid core of neuroepithelium (tail bud) during secondary neurulation.
* Ectodermal cells progressively disconnect- ing from the lateral walls of the neural folds during formation of the neural tube differentiate into the neural crest cells (form branchial arch derivatives, dorsal roots/ dorsal root ganglia, autonomic ganglia and adrenergic cells).
* Disjunction: Immediately after neural tube closure it becomes separated from the over- lying superficial ectoderm (forms the skin) by dorsally migrating mesenchyme (forms meninges, neural arches of the vertebrae and paraspinal muscles).
Which one of the following statements about
secondary neurulation and retrogressive differentiation is most accurate?
a. Important for the formation of the conus
medullaris but not the filum terminale
b. Involves canalization of a caudal mensenchymal cell mass
c. Is completed by days 24-26 of embryonic
development
d. Responsible for the formation of thoracic,
lumbar, sacral, and coccygeal neural tube
e. Retrogressive differentiation is a mitotic
process
b. Involves canalization of a caudal mensenchymal cell mass
The location of the caudal end of the neural plate (posterior neuropore) is approximately at the S3 level. The remaining caudal sacral and coccygeal portions of the neural tube, including the conus medullaris and filum terminale are formed by sec- ondary neurulation and retrogressive differentia- tion (days 28-48). During secondary neurulation, a secondary neural tube is formed caudad to the posterior neuropore. A caudal cell mass of undif- ferentiated, totipotential cells initially appears as a
result of fusion of neural ectoderm with the lower portion of the notochord. Multiple small vacuoles then appear in the caudal cell mass and progres- sively coalesce to form a central canal (canaliza- tion), which will merge with the canal formed during primary neurulation. Retrogressive differ- entiation is an apoptotic process in which a com- bination of regression, degeneration and further differentiation of the caudal cell mass into the tip of the conus medullaris, ventriculus termina- lis, and filum terminale.
Which one of the following statements about
ventral induction is most accurate?
a. It includes development of the primary
brain fissure
b. It includes development of the secondary brain vesicles and brain flexures
c. It includes formation of the neural plate
d. It includes formation of the notochord
e. It includes primary neurulation
b. It includes development of the secondary brain vesicles and brain flexures
By the end of dorsal induction/primary neurulation the neural tube is closed and three primary brain vesicles (prosencephalon, mesencephalon, and rhombencephalon) are present. During ventral induction (5th-10th weeks of gestation) the pri- mary brain vesicles differentiate into five secondary brain vesicles by day 35 (telencephalon, dience- phalon, mesencephalon, metencephalon, and mye- lencephalon) which then form forebrain, midbrain, and hindbrain structures. Between the 4th and 8th weeks, the brain tube folds sharply at three loca- tions. The first of these folds to develop is the cephalic flexure (between diencephalon and mes- encephalon), followed by the cervical flexure between myelencephalon and spinal cord—both flexures are ventral and produce an inverted U shape. The last flexure is dorsally located between metencephalon and myelencephalon (pontine flex- ure) and changes the shape to an M. By the 8th week, deepening of the pontine flexure has folded the metencephalon (including the developing cer- ebellum) back onto the myelencephalon. Any insult during this phase affects the development of brain vesicles and the formation of the facial skeleton. Ocular and nasal anomalies are frequently associ- ated with forebrain malformation because the optic placode and forebrain develop at the same time, with subsequent formation of the olfactory vesicle 1 week later. The commonly seen forebrain ventral induction malformations are (1) holoprosence- phaly, (2) atelencephaly, (3) olfactory aplasia, (4) agenesis of the corpus callosum, and (5) agenesis of the septum pellucidum (septo-optic dysplasia, cavum vergae and pellucidum). Hindbrain anoma- lies include vermian dysgenesis (e.g., Dandy- Walker spectrum).
The disencephalon does not give rise to which one of the following?
a. 3rd ventricle
b. Mamillary bodies
c. Optic vesicle
d. Posterior pituitary
e. Superior colliculus
c. Optic vesicle
The prosencephalon is the most rostral of the three brain vesicles and gives rise to a caudal dien- cephalon and a rostral telencephalon. A pair of diverticula, known as the telencephalic vesicles,
appear dorsally and rostrally, which form the cerebral hemispheres as the central cavities form the lateral ventricles. The posterior part of the prosencephalon becomes the diencephalon, which later develops into the thalami, hypothala- mus, epithalamus, optic cups, and neurohypoph- ysis. The central cavity in the region of diencephalon forms the third ventricle. Simulta- neously, two lateral outpouchings (optic vesicles) grow from the telencephalon on each side. These optic vesicles form the retina and optic nerve. Cells of the diencephalon and telencephalon originate from the germinal matrix lining of the third and lateral ventricles, respectively. The tel- encephalon grows rapidly and covers the devel- oping diencephalon, midbrain and hindbrain, because the outer regions grow more rapidly than the floor. This growth of the cerebral hemi- spheres within the developing cranial cavity gives the characteristic “C” shape to the developing lat- eral ventricles. The mesenchymal tissue trapped in the midline between the developing hemi- spheres develops into the cerebral falx.
Mesencephalon does NOT give rise to which one of the following?
a. Cerebral aqueduct
b. Edinger-Westphal nucleus
c. Pineal body
d. Red nucleus
e. Substantia nigra
c. Pineal body
The mesencephalon undergoes the least amount of change during the expansion from three pri- mary to five secondary brain vesicles, and forms the midbrain. The central cavity decreases in size to form the aqueduct of Sylvius. The neuroblasts from the dorsal alar plates migrate and appear as two swellings that form the superior and inferior colliculi (tectal plate). Some cells of the alar plate also migrate ventrally to form the red nucleus and substantia nigra. The basal plate of the mesen- cephalon forms the midbrain tegmentum (which include the somatic and general visceral efferent columns, and crus cerebri).
Which one of the following statements about
the rhombencephalon is most accurate?
a. It contains the cerebral aqueduct at
its center
b. It gives rise to diencephalon and myelen-
cephalon secondary brain vesicles
c. It gives rise to the inferior colliculi and pons
d. It is separated from the mesencephalon by
the isthmus rhombencephalii
e. Pontine flexure indents the rhomben-
cephalon ventrally
d. It is separated from the mesencephalon by
the isthmus rhombencephalii
With rapid growth of the embryonic brain, the neu- ral tube bends on itself in a zigzag fashion. Two flex- ures developed initially are the cephalic and the cervical flexures, and these are concave ventrally so the neural tube forms a wide upside-down U-shaped configuration. The mescencephalon and rhombencephalon are separated by a constric- tion (isthmus rhombencephalii). Around 6 weeks of gestation, the pontine flexure develops dorsally between the two rhombencephalic vesicles— metencephalon (future pons and cerebellum) and myelencephalon (future medulla). This flexure is concave dorsally, thereby converting the shape of the developing neural tube into a broad “M” shape. Hindbrain structures form as follows:
* Pons—develops from a thickening in the floor and lateral walls of the metencephalon.
* Medulla oblongata—develops from the thickened floor and lateral walls of the mye- lencephalon which is continuous inferiorly
with the spinal cord.
* Cerebellum—alar plates of the and rhombic
lips of the metencephalon form the cerebellum.
Which one of the following statements about
cerebellar development is most accurate?
a. Brainstem input to the cerebellum is via
parallel and climbing fibers
b. Commences at week 15
c. Golgi cells come to reside in the
molecular layer
d. Granule cells develop axons called Mossy
fibers
e. Granule cells migrate inward past Purkinje cells with the help of Bergmann glia
e. Granule cells migrate inward past Purkinje cells with the help of Bergmann glia
Development of the pontine flexure result in:
* Thecranialandthecaudalendsofthe4th
ventricle approximate together dorsally.
* The rhombencephalic roof plate is folded inward towards the cavity of the 4th
ventricle.
* The alar columns are splayed laterally
because of the bending of the pons and eventually lie dorsolateral to the basal columns.
Therefore, the roof plate of the developing 4th ventricle remains thin, is wide at its fold/waist and tapers superiorly and inferiorly (diamond shaped). Mesenchyme inserts itself into the roof fold and forms the plica choroidalis (choroid plexus precur- sor) which divides the roof of the 4th ventricle into a superior anterior membranous area (AMA) and inferior posterior membranous area (PMA). The alar laminae along the lateral margins of the AMA become thickened to form two rhombic lips, which enlarge to approach each other and fuse in the midline dorsally (covering the rostral half of the 4th ventricle and overlapping the pons and the medulla). As the rhombic lips grow to form the cer- ebellar hemispheres and midline vermis, the AMA regresses by incorporation into the developing choroid plexus. Growth and backward extension of the cerebellum pushes the choroid plexus inferi- orly, whereas the PMA greatly diminishes in the relative size compared with the overgrowing cere- bellum. Subsequently there is development of a marked caudal protrusion of the 4th ventricle, caus- ing the PMA to expand as the finger of a glove. This Blake’s pouch consists of ventricular ependyma sur- rounded by condensation of the mesenchymal tis- sues and is initially a closed cavity that does not communicate with the surrounding subarachnoid space of the cisterna magna. The network between the vermis and the Blake’s pouch progressively becomes condensed, whereas the other portions about the evagination become rarified resulting in permeabilization of the Blake’s pouch to form the foramen of Magendie. The foramina of Luschka also probably appear late into the 4th month of ges- tation. From superior to inferior, the residual AMA,
choroid plexus and residual PMA (i.e., residual rhombencephalic roof plate) form the definitive tela choroidea of the 4th ventricle. Folding, trans- verse fissure formation and foliation result in anterior lobe (cerebellar vermis and hemisphere above primary fissure), posterior lobe (vermis and hemispheres below primary fissure) and a flocculonodularlobe.
Development of the cerebellar cortex and deep nuclei (dentate, globose, emboliform, and fasti- gial) occurs as follows:
* Week 8—Metencephalon consists of typical ventricular, mantle and marginal layers and rhombic lips have started to form the cere- bellum. The ventricular layer produces four types of neurons forming the mantle layer which will subsequently migrate to the cor- tex: Purkinje cells, Golgi cells, basket cells, and stellate cells, as well as their associated glia (astrocytes including Bergmann glia, and oligodendrocytes).
* Week 12—Two additional layers form: an external germinal/granular layer derived from the rhombic lips, from which granular cells migrate inwards to form a new internal germinal layer between the ventricular and marginal layers (cells of the mantle layer have now dispersed into the marginal layer where they will form a distinct cortical pat- tern). External germinal layer also produces primitive nuclear neurons which also migrate inwards to form the deep cerebellar nuclei. Migration of granule cells takes place along Bergman (radial) glia. Purkinje cells migrate toward the cortex, it reels out an axon that maintains synaptic contact with neurons in the developing deep cerebellar nuclei. These axons will constitute the only efferents of the mature cerebellar cortex.
* Week15—Fromsuperficialtodeepthecere- bellum consists of: external granular layer (persists until approximately 15 months post- natally), Purkinje cell layer, molecular layer (stellate, basket cells), and granular layer (Golgi cells; granule cells and their parallel fibers), white matter (Mossy fibers from brain- stem nulcei, climbing fibers from inferior olivary nucleus) and deep cerebellar nuclei.
Which one of the following best describes cells forming the mantle layer in the developing neural tube?
a. Ependymal cells
b. Glioblasts
c. Neuroblasts
d. Postmitotic young neurons
e. Radial cells
d. Postmitotic young neurons
Except in the telencephalon, neurogenesis establishes the following architecture of the neural tube (from central to peripheral):
1. Central canal.
2. Ventricular layer—neuroepithelial (radial)
cells which give rise to all other layers.
3. Mantle layer—contains cell bodies of post- mitotic young neurons which have migrated laterally from the ventricular layer
and will form eventual gray matter.
4. Marginal layer—outermost layer contains the axons of neurons in the mantle layer, and will form eventual white matter
(folding of the cerebral hemispheres will
alter its position to subcortical).
After production of neurons is waning in the ven- tricular layer, this layer begins to produce a new cell type, the glioblast which differentiate into glia of the CNS—astrocytes and oligodendrocytes. Glia provide metabolic and structural support to the neurons of the central nervous system. The last cells produced by the ventricular layer are the ependymal cells; these line the brain ven- tricles and the central canal of the spinal cord and produce CSF.
Which one of the following statements about cerebral cortex formation is most accurate?
a. Cortical layers are laid down from most superficial to deep
b. Germinal matrix zone is superficial to the ventricular zone
c. Intermediate zone contains axons of cortical pyramidal neurons
d. Migration of cortical pyramidal neurons occurs tangentially
e. The neocortex usually has four layers in the adult
c. Intermediate zone contains axons of cortical pyramidal neurons
The cerebral cortex is made up of several cell layers (or laminae) that vary in number from three in the phylogenetically oldest parts to six in the dominant neocortex. Compared to the rest of the CNS, cerebral cortex has an “inside-out” arrangement of gray and white matter.
* Proliferating cells of the ventricular layer undergo a series of regulated divisions to produce waves of neurons that migrate peripherally (on radial cell processes span- ning the full thickness of the cortex) and establish the neuronal layers of the cortex. The first wave of neurons form a cortical layer is termed the preplate.
* Axons extend from preplate cells back towards the ventricular zone producing an intermediate zone (white matter).
* As neurogenesis proceeds, new neurons are increasingly formed in an accessory ger- minative zone lying deep to the ventricular zone, called the subventricular (germinal matrix) zone.
* Multiple cortical layers are laid down in a sequence from deep to superficial, that is, the neurons of each wave migrate through the preceding layers to establish a more superfi- cial layer. This is thought to be mediated by reelin (glycoprotein) secreted by transient Cajal-Retzius cells which migrate to the marginal layer (lamina I) tangentially after being born in a dorsal midline telencephalic structure. As such, after normal cortical histo- genesis has been achieved in principle, only lamina II-VI persist in the adult.
* As the production of neurons tapers off, the ventricular layer gives rise to various kinds of glia and then to the ependyma.
More numerous but smaller than the pyramidal neurons are the inhibitory interneurons—the gran- ule cells, which originate in the ganglionic emi- nences of the ventral telencephalon and migrate dorsally into the cortex via a tangential route.
Which one of the following is the first to form in the developing brain?
a. Anterior commissure
b. Genu of corpus callosum
c. Hippocampal commissure
d. Posterior commissure
e. Splenium of corpus callosum
a. Anterior commissure
The commissures that connect the right and left cerebral hemispheres form from a thickening at the cranial end of the telencephalon, which rep- resents the zone of final neuropore closure. This area can be divided into a dorsal commissural plate and a ventral lamina terminalis:
* 7th week—anterior commissure forms in the commissural plate and interconnects the olfactory bulbs and olfactory centers of the two hemispheres.
* 9th week—hippocampal (forniceal) com- missure forms between the right and left hippocampi.
* 9th week (late)—corpus callosum linking together the right and left neocortices along their entire length. The most anterior part (the genu) of the corpus callosum appears first, and its posterior extension (the sple- nium) forms later in fetal life.
Which one of the following statements about the developing spinal cord are most accurate?
a. Alar columns form the intermediolateral
horn
b. Alar columns form the ventral horns
c. Dorsally the floor plate marks where the
paired basal columns meet
d. Laterally, the alar and basal plates abut at a groove called the sulcus limitans
e. Ventrally the roof plate marks where the
paired alar columns meet
d. Laterally, the alar and basal plates abut at a groove called the sulcus limitans
Cell bodies in subependymal zone: in the spinal cord cells remain near the subependymal zone to form the central gray matter of the spinal cord (mantle layer) and extend axonal processes toward the periphery of the spinal cord.
Axons (white matter) surrounds gray: the sur- rounding spinal cord white matter is comprised of local and ascending white matter tracts generated in the spinal cord gray matter and descending tracts from supranuclear sources.
Starting at the end of the 4th week, the neurons in the mantle layer of the spinal cord become organized into four plates that run the length of the cord: a pair of dorsal (alar) columns and a pair of ventral (basal) columns. Laterally, the two plates abut at a groove called the sulcus limitans, dorsally the roof plate and ventrally the floor plate (both non-neurogenic). The cells of the ventral columns become the somatic motoneurons of the spinal cord and innervate somatic motor struc- tures such as the voluntary (striated) muscles of the body wall and extremities. The cells of the dorsal columns develop into association neurons receiving synapses from afferent (incoming) fibers from the sensory neurons of the dorsal root gang- lia, and either synapsing with ipsilateral/contralat- eral motoneurons to form a reflex arc or it may ascend to the brain. The outgoing (efferent) motor neuron fibers exit via the ventral roots. In most regions of the cord—at all 12 thoracic levels, at lumbar levels L1 and L2, and at sacral levels S2- S4—the neurons in more dorsal regions of the ventral columns segregate to form intermediolat- eral cell columns. The thoracic and lumbar
intermediolateral cell columns contain the visceral motoneurons that constitute the central auto- nomic motoneurons of the sympathetic division, whereas the intermediolateral cell columns in the sacral region contain the visceral motoneurons that constitute the central autonomic motoneu- rons of the parasympathetic division.
