SA_chap2

Question 1

What are the stages of CNS development

Answer 1

Blastogenesis, gastrulation, dorsal induction, ventral induction, neural proliferation, neuronal migration and then axonal myelination.

Question 2

Blastogenesis

Answer 2

Days 1-13

Development from a fertilized embryo ito a bilaminar blastocyst implanted in the uterus with amniotic and yolk sacs

Question 3

Gastrulation

Answer 3

Gastrulation occurs from day 14-17. During gastrulation the bilaminar disc is converted into a trilaminar disc including integration of bilateral notochordal anlagen into a single notochordal process and segmental notochordal formation.

Question 4

Dorsal induction

Answer 4

Dorsal induction Day 17-28. Formation and closure of the neural tube by primary neurulation. The three primary brain vesicles develop during this period. The mesecephalic flexure develops by day 21 and the cervical flexure develops by day 28. The pontine flexure forms on day 32.

Question 5

Secondary neurulation

Answer 5

Secondary neurulation occurs during day 28-48. At this time the neural tube caudal to the posterior neuropore is formed from mesenchyme by cavitation.

Question 6

Ventral induction

Answer 6

Ventral induction occurs during the 5th to 10th week. The three primary brain vesicles - prosencephalon, mesencephalon and rhombencephalon - differentiation into five vesicles.

Prosencephalon into telencephalon and diencephalon. The rhobencephalon into the metencephalon and myelencencephalon. The mesencephalon stays as is.

Question 7

Neuronal proliferation and migration

Answer 7

Neural proliferation occurs during weeks 6-12. Neuroblasts proliferate in the subependymal zone of the neural tube adjacent to the central canal of the spinal cord or the ventricles of the brain. Neuronal migration starts around week 8. Neurons use radial glial cell fibers as scaffolds to reach the cortical or subcortical layers.

Question 8

When do myelination, synaptogenesis and synaptic elimination occur.

Answer 8

Myelination starts at 6 months and ends in adulthood.

Synaptogensis starts in week 20.

Synaptic elimination starts 12 months postnatally.

Question 9

Defects in gastrulation cause:

Answer 9

Defects in gastrulation will affect the development and differentiation of all three primary cell layers and cause abnormalities from the occiput downwards including:

1. Split cord malformations
2. Spina bifida
3. Dermoid and epidermoid cysts.
4. Neurenteric cysts
5. Intestinal duplication
6. Anterior meningoceles

Question 10

The primitive streak forms when?

Answer 10

Day 14-15. Thus it forms during gastrulation.

It arises from thickened epiblast/ectoderm.

Question 11

Dorsal induction includes what processes

Answer 11

Primary and secondary neurulation. The formation of the true notochord and neural tube.

Question 12

Fusion of the neural tube first occurs where

Answer 12

At the level of the 4th somite which represents the future CCJ.

Question 13

The anterior and posterior neuropores close when

Answer 13

Day 24-26 and 26-28 respectively. The former will give rise to the lamina terminalis. The latter does not actually represent the most caudal aspect of the spinal cord. That is formed during secondary neurulation.

Question 14

The neural crest gives rise to

Answer 14

Branchial arch derivatives

Dorsal Roots

Dorsal Root Ganglia

Autonomic ganglia

Adrenergic cells

Note that the neural crest is formed from the edges of the neural folds during closure to form the neural tube.

Question 15

What is disjunction

Answer 15

Occurs after neural tube closure and is the separation of the overlying superficial ectoderm from dorsally migrating mesenchyme which forms meninges and the neural arches of the vertebrae and paraspinal muscles.

Question 16

The lower sacral and coccygeal components of the neural tube are formed during

Answer 16

Secondary neurulation. Days 28-48. This involves canalization of a caudal mesenchymal mass and retrogressive differentiation of the rest of the mass into the tip of the conus medullaris and filum terminale.

Question 17

The three primary brain vesicles are formed during

Answer 17

Dorsal induction

Question 18

What are the three developmental flexures

Answer 18

The cephalic, cervical and pontine flexures.

The first two are ventral, while the pontine flexure is dorsal in nature. The cephalic flexure occurs first between the diencephalon and mesencephalon. The cervical between the myelencephalon anf spinal cord. The pontine between the metencephalon and myelencephlon.

These flexures are all formed by te 8th week.

Question 19

Disorders of ventral induction result in

Answer 19

Holoprosencephaly, olfactory aplasia, agenesis of the corpus callosum, agenesis of the septum pellucidum, septo-optic dysplasia and vermian dysgenesis/Dandy Walker spectrum disorders.

Question 20

The diencephalon gives rise to

Answer 20

The thalamus, hypothalamus, epithalamus, optic cups, mamillary bodies, and neurohypophysis

Question 21

Migration of granule cells of the cerebellum takes place along

Answer 21

Bergman radial glia

Question 22

Mossy fiber input is from

Answer 22

brainstem nuclei

Question 23

Climbing fiber input is from

Answer 23

Inferior olivary nuclei

Question 24

The cerebellum develops between weeks

Answer 24

8-15

Question 25

What are the roles of SHH, Wnt, FGF8 and BMP4/7 in development

Answer 25

SHH: secreted by the notochord and floor plate - downregulates PAX3 and 7 expression in the midline and ventral half of the neural tube. Dorsoventral patterning.

Wnt - dorsoventral patterning. Active in the midline and dorsal portion of the neural tube.

FGF8 - secreted by the anterior neural ridge and induces brain factor 1 expression to induce telencephalon formation.

BMP4/7 maintain PAX expression in the dorsal neural tube and promote alar plate formation.

Question 26

What are the four major layers in the developing neural tube

Answer 26

Central Canal

Ventricular layer - produces neural cells, then glia then ependymal cells. All other layers come from this layer

Mantle layer - contains post-mitotic neurons, will form the gray matter

Marginal layer - contains axons of neurons, will form the white matter. Initially the outermost layer, developmental folding will take it subcortical in position.

Question 27

Commisural formation

Answer 27

Commissural formation takes place from weeks 7-9. The commissures form from the commissural plate which is a thickening at the cranial end of the telencephalon. The anterior commissure forms first, then the hippocampal commissure then the corpus callosum (genu first, splenium last)

Question 28

The spinal cord grey matter is formed form neurons within the ______ layer during embryogenesis

Answer 28

Mantle layer

Question 29

Neurons in the mantle layer of the developmental spinal cord develop into …..

Answer 29

In week 4 the neurons in the mantle layer of the spinal cord develop into the alar columns dorsally and the basal columns ventrally. These meet laterally at the sulcus limitans, dorsally the alar columns form the roof plate and ventrally the basal columns form the floor plate.

Question 30

The alar columns become..

Answer 30

The alar columns which are dorsal will eventally become the association neurons, receive afferent neurons and develop reflex arcs.

Question 31

The basal columns develop into

Answer 31

The basal columns which are ventral will eventually become the somatic motor neurons

Question 32

The intermediolateral cell columns develop from

Answer 32

The dorsal most aspect of the ventral columns to give rise to the autonomic system

Question 33

The adenohypophsis originates from what

Answer 33

A diverticulum called the infundibulum develops in the floor of the third ventricle and grows ventrally to the stomodeum - ectodermal lined future mouth opening.

Simultaneously an ectodermal thickening/placode from the roof of the stomodeum invaginated to form a diverticulum - Rathke’s pouch - which grows towards the infundibulum. This will ultimately lose its connection with the stomodeum and appose the infundibulum

The anterior portion becomes the adenohypophysis, the posterior portion becomes the pars intermedia.

Question 34

Embyrologically the brainstem nuclei result from which columns?

Answer 34

There are four brainstem colums - two basal/medial columns and two alar/lateral columns.

The basal columns are responsible for GSE, SVE, and GVE (medial to lateral). GSE = extrinsic ocular muscles and muscles of the tongue. SVE/branchial efferent - striated muscle derived from neural crest, 5/7/9/10/11. GVE - parasympathetic outflow - 3,9,10 - EW nuclei, salivatory nuclei and the dorsal vagal motor nuclei.

The alar columns are lateral and are responsible for GVA, SVA, SSA, GSA.

GVA - cranial nerve 10 - thoracoabdominopelvic viscera sensation.

SVA - taste 7 and 9

SSA - hearing and balance - 8

GSA - somatic sensation from the head and neck, 5,7,9, 10.

Question 35

The germinal matrix has high levels of

Answer 35

Tissue plasminogen activator. Explains why it has a high hemorrhage risk.

Question 36

When do the fontanelles close.

Answer 36

There are six fontanelles. Anterior, posterior and bilateral sphenoid and mastoid.

The posterior closes at 3 months

The sphenoid at 6 months.

The mastoid at 6-18 months

The anterior by 7-19 months

Question 37

The main function of the notochord is to

Answer 37

Initiate neurulation

Question 38

What are somites

Answer 38

Transient segmented structures which are derived from the paraxial mesoderm and contain progenitors of the axial skeleton, trunk musculature, endothelial cells, smooth muscle cells, brown adipose tissue and meninges

Question 39

Somites undergo what transformation

Answer 39

Shortly after forming somites undergo a epithelial to mesenchymal transformation to form the sclerotome ventromedially - this is the future vertebrae and ribs, while the dorsal part forms the dermomyotome which is the future skin and muscle.

Question 40

The vertebral body arises from the ….

The vertebral arch and spinous process arises from the …

Answer 40

Sclerotome

Dermomyotome

Question 41

Sclerotomes

Answer 41

The sclerotome arises from the ventromedial portion of the somites and gives rise to the vertebral body. It is divided into cranial and caudal portions by an intersegmental boundary known as von Ebner’s fissure. The caudal portion is denser and cells can only migrate to the cranial portion of the sclerotome which allows for segmenation of the peripheral nervous system.

Sclerotomes will eventually split along von Ebner’s fissure and the caudal segment of each sclerotome fuses with the adjacent cranial segment to form a vertebrae. This is known as resegmenation

Question 42

Nucleus pulposos has a ……origin.

Annulus fibrosis has a …..origin

Answer 42

Notochord

Sclerotomal