DeLahunta Chapter 3 - Embryology

Question 1

From which embryonal layer (layer and derm) do the following cells originate?
Neurons
Oligodendrocytes
Schwann cells
Microglia
Astrocytes

Answer 1

Neurons = neuroectoderm
Oligodendrocytes = neuroectoderm
Schwann cells = neural crest
Microglia = mesoderm (monocytes)
Astrocytes = neuroectoderm

Question 2

What cells are responsible for postnatal neurogenesis? In which areas of the adult brain can they be found?

Answer 2

Radial glial cells
-Rostral cerebral subventricular zone (especially olfactory bulb)
-Subgranular zone of the dentate gyrus of the hippocampus

Question 3

Name two cytokines important in establishing the dorsal/ventral neuroaxis, and from where do they originate?

Answer 3

1) Bone morphogenetic protein 4 (BMP4) originates from the overlying surface ectoderm –> developes the dorsal neural tube

2) Sonic hedgehog protein (SHH) from the underlying notochord –> developes the ventral neural tube

Question 4

Which structures originate from the neural crest cells?

Answer 4

1) dorsal root ganglia
2) melanoblasts/melanocytes
3) adrenal medullary cells
4) odontoblasts
5) enteric nervous system (glial cells in wall of bowel, interneurons, ganglionic parasympathetic portion of GVE LMN)
6) sympathetic trunk
7) cardiac septae (walls of great vessels at the base of heart)
8) parasympathetic neurons of urogenital system
9) bone & cartilage of the skull and derivaties of brachial arches
10) lemmocytes (Schwann cells) - myelin of PNS
11) thyroid parafollicular cells (C)
12) a portion of the leptomeninges

Question 5

Regarding supracollicular fluid accumulation, compression of which structure/s is most likely to lead to clinical signs? What degree of occipital lobe compression is more likely to cause clinical signs? (https://pubmed.ncbi.nlm.nih.gov/17939559/)

Answer 5

-Compression of both the occipital lobe and cerebellum together is more likely to cause clinical signs

-Occipital lobe compression of >14% is more likely to cause signs

Question 6

What structure separate the neopallium from the paleopallium?

Answer 6

The rhinal sulcus

Question 7

What toxins are associated with holoprosencephaly?

Answer 7

1) Griseofulvin in pregnant cats

2) Veratrum californicum in ewes at day 14-15 of pregnancy (contains alkaloid cyclopamine - interferes with SHH in precordal plate)

Question 8

Corpus callosum hypoplasia:
What breed/breeds appear overrepresented?
What are the most common clinical signs?
What other cortical malformation is this commonly seen with?

Answer 8

-Miniature Schnauzer & SBT
-Semiology: seizures, tremors, hypodipsia/hypernatremia
-Concomitant: lobar holoprocencephaly

https://pubmed.ncbi.nlm.nih.gov/24839863/

Question 9

What viruses can cause hydranencephaly?

Answer 9

1) Blutongue virus (sheep and cattle) at 1st trimester of pregnancy [otherwise if later causes porencephaly or very later no malformation just mild encephalitis] [signs: lameness, fever, oronasal ulcers]
2) BVD virus (cattle)
3) Akabane virus (rumminants; Jasapn, israel, australia) [we see arhtrogryposis]
4) Feline panleukopenia virus - FPV (cats) - but rare manifestation as cerebellar issues most common

Question 10

In which breeds is lissencephaly reported (dog and cat)

In which species a genetic mutation of lissencephaly + cerebellar hypoplasia complex has been found?

Answer 10

Small chinese dogs:
1) Lhasa apso
2) Shih Tzu (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305484/)
3) Pekignese (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658562/)
but also in crossbreeds

cats
1)Korat cats

Along with other malformations - susp. RELN genetic mutation from humans:
-wire fox terriers
-irish setters
-samoyed
but proven in:
White Swiss Terriers (https://pubmed.ncbi.nlm.nih.gov/37334487/)
& sheep (Dorset-cross) (https://journals.sagepub.com/doi/abs/10.1177/03009858241283501)

Question 11

What is the different between diplomyelia and diastematomyelia?

Answer 11

Diplomyelia is duplication of the spinal cord within the same dura.

Diastematomyelia is when there are two spinal cord which are each present within their own meningeal sheath and bony partition (vertebral canal)

Question 12

In what breed has “spinal dysraphism” (inherited myelodysplasia of that breed) been reported are an inherited condition? What gene is responsible for this?

Answer 12

-Misnormer
-In Weimaraner
-NKX2-8 gene mutation
-Complex malformation including other signs and organs
-abberation of any kind of canal/fissure
-scattered neurons across the midline

Question 13

At what day post partum should normal gyrification be present at full in dogs?

Answer 13

-born with few gyri
-gyrification occurs at 3-6 wo (De Lahunta)
-Day 14 post partum (https://pubmed.ncbi.nlm.nih.gov/22742068/)

Question 14

Regarding the normal brain maturation of MRI, at what age should a complete corpus callosum be visible on T2W in dogs? (https://pubmed.ncbi.nlm.nih.gov/20806866/)

Answer 14

2 month old (8 weeks) (https://pubmed.ncbi.nlm.nih.gov/20806866/)

Question 14

Regarding normal brain maturation on MRI:
a) How is the T1W and T2W of the white matter of a brain of a puppy at birth?
b)The relative grey-white matter signal intensities is reversed compared with the adult. At what age is the isointense transition period in T1W and T2W images in dogs?
c) Why this happens?

Answer 14

a) WM is hyperintense in T2W and hypointense in T1W compared to the GM

b)
at 3-4 weeks on T1W
at 4-8 weeks on T2W

c) Due to decrease of water content during myelination as the pup is growing up.

(https://pubmed.ncbi.nlm.nih.gov/20806866/)

Question 15

What is the alar plate and basal plate of the neural tube?

Answer 15

Alar plate: Dorsal portion of the neural canal (sensory systems)
Basal plate: Ventral portion of the neural canal (motor systems)

Question 16

From which embryological structures the cerebellum does develop?

Answer 16

Rhombic lip (= proliferation of germinal layer of alar plate)

Question 17

Which is the rostral boundary of the brainstem?

Answer 17

lamina terminalis

Question 18

Which are the types of fibers in the brain?

Answer 18

1) association fibers - connecting two areas within the same hemisphere
2) commissural fibers - connecting two hemispheres
3)projection fibers - connecting the hemishpere with brainstem or rarely with spinal cord

Question 19

What is anencephaly? In which species it has been reported?

Answer 19

=Lack of cerebral hemispheres (rest of brain is usually spared, maybe can be dysplastic)

-accompanied by cranioschisis

-in CALVES e.g. Guernsay (alternative name: cerebral/telencephalic hypoplasia/aplacia)

Question 20

What is meningocele or meningoencephalocele?
Which are the two most common causes of this in cats?

Answer 20

-Protruding (herniation) of cerebral/meningeal tissue through a calvarian defect and covered by skin.

-requires cranioshisis

-this is the most common malformation

-cats:
1) kittens that the mother was treated with griseofulvin during pregnancy

2)part of inherited craniofacial malformation in BURMESE cats with shortened face

Question 21

What is the most common brain malformation in animals?

Answer 21

meningocele/meningoencephalocele

Question 22

What is exencephaly?

Answer 22

=brain tissue protruding out of cranial cavity not covered by skin but by connective tissue of meninges

-requires cranioschisis

Question 23

What is lipomeningocele?

Answer 23

=meningocele associated with fat content

-requires cranioschisis

-can occur in the spine as well

-not associated with neural tube malformation - so no neuro signs

-reported in CALVES in the book

Question 24

What is diprosopus/dicephalus?

Answer 24

=duplication of prosencephalon
but the brainstem is single at midbrain level

-Reported in CALVES…

Question 25

What is Holoprosencephaly?
a) Which are 2 clinical signs that can accompany holoprosencephaly?
b) Which toxic causes can cause holoprosencephaly in which animals?
c) It has been reported without orofacial abnromalities - in which speacies and breeds?

Answer 25

=failure of prosencephalon to develop into 2 hemispheres

a) usually associated with cyclopean eye + dorsal proboscis

b) -griseofulvin in mother of kittens
-Veratrum californicum in lambs in 14-15d of pregnancy (alkaloid cyclopamine –> interfere to SHH pathway)

c) Dogs
- Miniature Schnauzer & Staffies- lobar holoprocencephaly +/- corpus callosum dysplasia
-Horse: Morgan Horse - semilobar holoprocencephaly

Question 26

Which are the types of holoprosencephaly based on the development of the longitudinal cerebral fissure?

Answer 26

1) Alobar - no fissure
2) Semilobar - only little fissure
3) Lobar - some kind of fisssure but not normal

Question 27

What is hydrancencephaly?
What is the pathologenetic cause of it?

Answer 27

=Absent cerebral hemishperes filled with CSF (covered by thin layer of ependyma in the ventricle level)

Causes: Loss of neopallial parenchyma (paleopallium/archipalium are spared) due to:
1) aplasia due to viral destruction of germinal layer
2) atrophy due to viral destruction of already differentianted neurons
3) destruction of vasculatlure and supply to he neopallium by the virus

Question 28

What is porencephaly?

Answer 28

=Fluid filled cavities in the cerebrum that communicate with the lateral ventricles

Question 29

What is lyssencephaly?
a) In which species and breeds it is more common as pathological?
b) which animals lyssencephaly is considered normal?
c) what is the suspected pathomechanism?

Answer 29

=Lack of gyri/sulci in the brain

a)
-Cats - KORAT
-Dogs - Lhasa apso (most common), but also other chinese like Shih Tzu, Pekignese
see other question about complex malformation in other dogs.

b) birds, rodents, rabbits/lagomorphs

c) impaired neuronal migration

Question 30

Which is the most common species for meningoencephalocele/meningocele?

Answer 30

Pigs

Question 31

What is polymicrogyria? Which dog species is the most common?

Answer 31

-multiple small gyri creating excessive folding of the brain leading to an abnormally thick cortex.

-Miniature or Standard poodle

(https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1002/vrc2.254; https://onlinelibrary.wiley.com/doi/full/10.1111/j.1939-1676.2009.0338.x#:~:text=Background%3A%20Polymicrogyria%20is%20a%20disorder,Standard%20Poodles%20and%20in%20cattle.)

Question 32

Which are the stages of developement of the neural tube?

Answer 32

Stage A: neural plate
Stabe B: neural groove
Stage C: neural tube & neural canal

Question 33

Which are the 3 concentric layers of the neural tube; where are they located in relationship to the canal; which cells originate from each layer?

Answer 33

inner to external:
germinal –> ependyma
mantle –> immature neurons (GM of SC, nuclei, basal nuclei cerebrocortex) & spongioblasts (glia - oligodendrocytes, astrocytes, excluding microglia)
marginal –> axons from the mantle (WM)

Question 34

What is the sulcus limitans? What is originated from the mantle layer of the sulculs limitans?

Answer 34

-is a longitudinal groove in the lateral wall of the central canal that divides neural tube to the alar plate (snesory) and basal plate (motor)

-the lateral gray horn

-

Question 35

Where do the different gray horns of the spinal cord originate from?

Answer 35

Mantle layer of:
1) alar plate –>dorsal gray horn
2) basal plate –> ventral gray horn
3) sulcus limitans –> lateral gray horn

Question 36

When and where does the unique one mitosis in CNS occurs?

Answer 36

-during emrybology
-in the mantle layer of the neural tube the immaure neuron becomes mautre neuron
-then neurogenesis no more.

Question 37

What is radial glia cells? Which is their function? Which is their clinical implication?

Answer 37

Radial glial cells=cell line from the embryonic neuroepithelial cells in the embryonic neural tube (radial astrocytes)

Functions:
1) guide the developed immaure neurons to the site of destination
2) postnatal differentiation to immature neurons, astroctyes, oligodendrocytes, ependumal cells (functioning as stem cells)

Clinicial implication:
-source of glioma
-role in plasticity of injury

Question 38

Which are the 3 primary and 5 secondary brain veiscles during brain formation?

Answer 38

3 primary:
-prosencephalon
-mesencephalon
-rhombencephalon

5 secondary:
-telencephalon (pros)
-diencephalon (pros)
-mesencephalon
-metencephalon (rhomb)
-myelencephalon (rhomb)

Question 39

What is neurobiotaxis?

Answer 39

Phenomenon of migration of the cells from the mantle layer to the are of a nucleus elsewhere.

Question 40

What is the centrum semiovale, the corona radiata, the internal capsule and external capsule and their differences?

Answer 40

All of them WM:
-Centrum semiovale: uppormost portion of WM in the hemisphere (superior of lateral ventrcile) - which contains all fibers (association, projection, commisural)
-Corona radiata: continuation of centrum semiovale dorsally (association & projection fibers)
-Internal capsule: continuation of corona radiata ventrally (projection fibers only)
-external capulse: assocaition fibers between claustrum and cortex (it is located between claustrum and putamen)

Question 41

Where do meningiomas arrise from in the ventricular system?

Answer 41

From the arachnoid cap cells associated with choroid plexus.

-They arise from the neural crest

-They are usually located in clusters on the apical surface of an arahcnoid villus that project into a venous sinous.

Question 42

How is holoprocencephaly alternativelly named and why?

Answer 42

arrhinencephaly as there is failure to develop the nasal portion of the respiratory/olfactory system

Question 43

What is a neuroendodermal cysts?

Answer 43

=cysts as a result of remant of disintegrating notochondral process and endonderm which are incorporated within the developing neural tube

Question 44

What is the notochord? which is its role?

Answer 44

It is a mesodermal structure ventrally to the neural tube.

role:
(a) singaling through SHH
(b) connecting with endoderm

Question 45

What is syringomyelia, hydromyelia and presyrinx oedmea?

Answer 45

-Syringomyelia: cavitation of SC
-Hydromyelia: dilatation of central canal
-Presyrinx oedema: is the T2W hyperintensity of the spinal cord in the absence of syringomyelia (mainly occuring in the less resistant dorsal funiculi)

Question 46

Why in C1 level we do not usually see syringomyelia?

Answer 46

Maybe due to Venturi effect, which means that due to smaller diameter of central canal at C2-3, there is less pressure higher velocity of the CSF

Question 47

We have a dog with R sided cervical scoliosis. In which side is the lesion?

Answer 47

To the L. The neck is bending away from the side of gray matter lesion.

Question 48

What defines an open fontanelle?

Answer 48

=incomplete ossification of the frontoparietal bone

Question 49

Which is the most common species (and their localisation) for spinal cord malformations?

Answer 49

CALVES
T3-L3 SCS

Question 50

What is a characteristic clinical sign of dogs with myelodysplasia? And how this is explained?

Answer 50

Bunny hopping gait
It is an abnormal reflex sign as a result of CPG dysfunction causing simultataneous ‘cross extensor reflex’ type of thing in both limbs

Question 51

What is spina bifida, rachioschisis, myeloschisis, and meningomyelocele?

Answer 51

-Spina bifida: Failure of the vertebral arch to develop/fuse
-Rachischisis: equal to spina bifida - when vertebral canal is not closed
-Myeloschisis: failure of neural tube to close

Question 52

Which species/breeds are predisposed to spina bifida and in which location?

Answer 52

-dog - english bulldog (lumboscaral spinal bidifa)
-cats - manx (sacrocaudal spina bifida)

Question 53

Where the masticatory muscles originate from embryologically?

Answer 53

mesoderm (somitomers of brachial arch I)