Lecture 1: Development

Question 1

When does myelination of axons occur during development

Answer 1

Postnatally by oligodendrocytes

Question 2

When does the most neuronal cell proliferation occur?

Answer 2

First 5 months since birth

Question 3

What causes the differentiation of different types of neurons (Eg. dopaminergic vs. GABAergic) and glial cells?

Answer 3

A plethora of different combinations and concentrations of various signalling molecules

Question 4

What are bone morphogenic proteins (BMPs)

Answer 4

Signalling molecules released by the ectoderm next to the neural groove which cause formation of the sensory neurons via the alar plate of the neural tube (dorsal part of the spinal cord)

Question 5

How many layers of neurons are there in the adult cerebral cortex?

How do they develop?

Answer 5

Cerebral cortex consists of 6 layers. They develop in an “inside out” fashion. Radial glial cells provide a scaffold (that extends from the ventricular surface to the pial surface) in which neuroblasts can migrate along.

1. The first cell layer to develop is layer 6 (which is the inner most layer). The cells migrate through the intermediate zone and past the subplate to arrive at the cortical plate.
2. The next group of cells migrate past layer 6 to become what becomes layer 5 and so on.
3. The last cells to migrate are layer 1

Question 6

What is meningomyelocele

Answer 6

The most severe case of spina bifida where elements of the spinal cord, cauda equina and meninges herniate through a defect in the vertebral column. Has severe consequences to motor function and sensation to lower limbs

Question 7

What are the 4 types of glial cells?

Answer 7

Astrocytes, oligodendrocytes, microglia and ependymal cells

Question 8

How is neuronal proliferation regulated? And when does this occur?

Answer 8

Neuronal proliferation occurs between 5 weeks to 5 months - and is regulated by two signalling molecules within the neuroblast

1. Notch-1 (sits on the pole of the neuron closest to the pial surface)
2. Numb (sits closest to the ventricular surface)

They occupy a polar position within the neuroblast (as above). When a neuroblast undergoes verticle cleavage - both notch-1 and numb are maintained. When a neuroblast undergoes horizontal cleavage, Notch-1 and Numb-1 are contained in separate daughter cells and the Notch-1 cell will migrate and be unable to proliferate (when notch-1 is expressed on its own it causes the migration to the pial surface).

Numb inhibits notch when contained in a single cell during vertical cleavage.

Question 9

When do secondary vesicles appear?

Answer 9

Weeks 5 to 6

Question 10

What are names of the vesicles in red, pink, green, blue and purple? and what do they give rise to?

What is 1, 2 and 3?

Answer 10

A. Telencephalon: Cerebral hemispheres, hippocamous, amygdala and basal ganglia

B. Diencephalon: thalamus, hypothalamus and retina

C. Mesencephalon: midbrain

D. Metencephalon: pons and cerebellum

E. Myelencephalon: medulla

1. Cervical flexure
2. Pontine flexure
3. Cephalic flexure

Question 11

How are neural crest cells formed?

Answer 11

As the neural folds come together, some neural ectoderm cells get pinched off to form neural crest cells

Question 12

What is the function of sonic hedgehog (SHH)

Answer 12

Cause differentiation of the cells which go on to form the ventral part of the spinal cord via the basal plate of neural tube(to form motor neurons)

Question 13

Which flexures of the primary vesicles exist in the adult?

Answer 13

The cervical flexure does not exist in the adult - it straightens out. The cephalic flexure still exists in the adult which is why there is an angle where the brain stem meets the cerebrum.

Question 14

What happens when the rostral end of the neural tube fails to develop?

Answer 14

Failure of the rostral end is a catastrophic developmental defect (anencephaly) where the foetus lacks much of the forebrain and cranium and results in death

Question 15

What causes spina bifida?

Answer 15

Spina bifida is a neural tube defect that results from the failure of the caudal end of the neural tube to close (and can vary in severity.

Question 16

Describe the formation of the neural groove

Answer 16

Midline mesoderm (notochord) releases signalling molecules that lead to the thickening of the overlying ectoderm to form the neural plate. The lateral edges of the neural plate become elevated and move together to form the neural fold. The neural fold moves inwards to form he neural groove. The neural groove eventually closes to form the neural tube

Question 17

What is different in the pattern of differentiation between that on other parts of the neural tube and the rhombencephalon

Answer 17

The neural tube develops in a dorsoventral gradient of sonic hedghog (basal plate, to form ventral spinal cord and motor neurons) and bone morphogenic proteins (alar plate to form dorsal spinal cord and sensory neurons)

The rhombencephalon develops in a rostrocaudal pattern of differentiation via FGF8 (rostral) and Retinoic Acid (caudal). Differential concentrations of these two signalling molecules causes a differing pattern of HOX genes to be transcribed. This results in the diffential pattern of development in the rhombencephalon. Resulting in rhombomeres which are segments of the rhombencephalon. Every rhombere is driven in its development by the expression of a different set of HOX genes. And its the differing concentrations of FGF8 and retinoic acid that results in different combinations of HOX genes. Note: this happens very early on in development, around day 29

Question 18

What is A, B and C?

Answer 18

The Primary Vesicles:

A. Prosencephalon

B. Mesencephalon

C. Rhombencephalon

Question 19

What is this image showing? What type of MRI is this?

Answer 19

This is a T2 weighted MRI, where CSF is bright and myelin is dark. This is showing that myelination of neurons occurs posnatally, and you can see the increased white matter 24 months since birth.

Question 20

Neuronal connections continue to form postnatally: TRUE/FALSE

Answer 20

true

Question 21

When does formation of the neural groove occur?

Answer 21

3rd week

Question 22

Which of the primary germ layers gives rise the the nervous system?

Answer 22

The ectoderm (also gives rise to the skin)

Question 23

What divides the alar and basal plate?

Answer 23

sulcus limitans

Question 24

What lines the ventricles (and neural tube)?

Answer 24

Ependymal cells (a type of glial cell)

Question 25

What does the neural tube become

Answer 25

Ventricular system

Question 26

1. What is 1 & 2
2. What are the sections in red, green and blue?

Answer 26

1. Cervical flexure
2. Cephalic flexure
3. Red: prosencephalon
4. Green: mesencephalon
5. Blue: rhombencephalon

Question 27

What happens to the dorsal/ventral (or alar/basal in the neural tube) orientation of the spinal cord at the level of the brain stem

Answer 27

It becomes medial/lateral - the basal plate (giving rise to motor neurons) becomes medial and the alar plate (giving rise to sensory neurons) becomes lateral. The sulcus limitans still acts as an important boundary between motor and sensory in the brainstem.

Question 28

What is the function of astrocytes?

Answer 28

Astrocytes have homeostatic functions, provide structural support, contribute to the blood brain barrier and play a role in response to injury

Question 29

What happens to the telencephalon and diencephalon during weeks 6 - 12 of development?

Answer 29

1. Basal part of the telencephalon thickens to form the precursor of the basal ganglia
2. Diencephalon thickens to form thalamus and hypothalamus.

The formation of the temporal and frontal lobes begin: each cerebral hemisphere assumees the shape of a great arc (or C-shape) around the insula. Parts of the hemisphere originally dorsal to the insula get pushed around to the temporal love (ie. hippocampus). This continues until 9 months (birth)

Question 30

What is the significance of the pontine flexure?

Answer 30

In the rhombencephalon at the level of the pontine flexure the formation of the 4th ventricle begins

Question 31

What is the function of microglia

Answer 31

Microglia are resident immune cells of the central nervous system and clear cellular debris via phagocytosis, also play a role in response to injury

Question 32

Where does fusion of the neural tube begin?

Answer 32

It begins in the middle extending in both rostral and caudal directions

Question 33

Why can’t you see the insula cortex from viewing the lateral surface of the brain

Answer 33

Because the other parts of the brain grow so much more and “envelop” that part of cortex

Question 34

When does most neuronal differentiation occur during development

Answer 34

Within 4-9 months

Question 35

Neural crest cells

Answer 35

Form the PNS - in particular the dorsal root ganglia, autonomic ganglia (ganglia of parasympathetic and sympathetic nervous system), form the glial cells of peripheral nervous system such as schwanne cells and satellite glial cells

Question 36

What is A, B, C, D & E and what structures do they give rise to?

What is structure 1 and what is the significance?

Answer 36

A. Telencephalon: Cerebral hemispheres, hippocamous, amygdala and basal ganglia

B. Diencephalon: thalamus, hypothalamus and retina

C. Mesencephalon: midbrain

D. Metencephalon: pons and cerebellum

E. Myelencephalon: medulla

1. Lamina Terminalis - a thin membrain at rostral tip of neural tube - it is the origin of the bridge between two hemispheres where bundles of interconnecting fibres begin to grow

Question 37

What causes dorsal and ventral patterns of differentiation in the spinal cord?

Answer 37

Gradients of differing signalling molecules (sonic hedgehog and bone morphogenic proteins) establish a functional organisation (alar and basal plate). This functional organisation persists in the adult spinal cord - alar (dorsal) derivatives become sensory neurons and basal (ventral derivatives become motor

Question 38

What happens to the cortex during weeks 31 - full term?

Answer 38

Increase of cortical convolutions to increase surface area

Question 39

Describe the formation of the primary vesicles

Answer 39

The rostral end of the neural tube swells to form the prosencephalon, mesencephalon and rhombencephalon

Question 40

What is the function of oligodendrocytes?

Answer 40

Myelination of axons

Question 41

What prevents the neuroblast from migrating away from the ventricular surface during proliferation?

Answer 41

A neuroblast contains both Notch-1 and Numb during vertical cleavage. Numb inhibits Notch-1 to prevent migration - and retaining two daughter cells that are able to continue to proliferate.

Question 42

How does neuronal proliferation occur?

Answer 42

Proliferation of neuroblasts from neural stem cells in the ventricular zone of the developing neural tube and brain. Cleavage plane during cell division determines their fate. During early development (5 weeks - 3 months) they undergo vertical cleavage, creating two daughter cells - these two daughter cells can continue to proliferate again and again. Vertical cleavage leaves greater capacity for neuronal proliferation. During later development (3 months onwards) cells split by horizontal cleavage - only one of the daughter cells can continue to proliferate and the other migrates to the pial surface. So you lose half the capacity to proliferate during horizontal cleavage.