Congenital Diseases Associated With The CNS

Question 1

What is the first step in CNS formation?

Answer 1

• The first step is the formation of the neural plate
• It’s folding gives rise to the neural tube
• The neural tube then differentiates into: The brain, Spinal cord, Cranial and spinal nerves, eyes and other sensory organs, neural crest

Question 2

What happens if there is defects in the neural tube formation?

Answer 2

Defects will affect some or all of these structures formed by the neural tube

Question 3

When does neuralation occur in humans?

Answer 3

Between weeks 3 and 4

Question 4

Describe the neural tube formation

Answer 4

• The neural plate is initially a flat sheet of cells located along the dorsal portion of the developing embryo
• In direct continuation of with the epidermis and exposed to the extra embryonic medium
• This sheet of cells will become a tube, and will end up being located inside the embryo

Question 5

What happens as the neural tube closes?

Answer 5

• It becomes patterned along the dorso-ventral and the rostro-caudal axes.
• This process is driven by secreted signalling molecules
• Which promotes the specification of different CNS structures along each axis

Question 6

List some of the gradual subdivisions of the neural tube along the rostro caudal axis

Answer 6

• Forebrain -> Telencephalon & Diencephalon
• Midbrain -> Mesencephalon
• Hindbrain -> Metancephalon & Myelencephalom

Question 7

Where does Congenital defects arise from?

Answer 7

Can arise from perturbation of different steps during CNS formation

Question 8

Briefly describe some of the defects

Question 9

Describe the closure of the neural tube (PART 1)

Answer 9

• The first step involves the elevation of the edges of a neural plate to form neural folds
• The formation occurs along the midline of what we call the neural group
• Which contains the pressure in everything left in your plate
• In subsequent stages of development, the neural faults will move further when we move towards the midline and they will fuse

Question 10

Describe the closure of the neural tube (PART 2)

Answer 10

• Essentially in this stage, you go from a flat structure to a folded structure in which the edges of the neural shape is fused together
• This process doesn’t happen simultaneously along the plate but at specific points
• The first point to start closing is on the edge between the hind brain and the spinal cord
• In this region, the closure progresses anteriorly and posterioirly

Question 11

Describe the closure of the neural tube (PART 3)

Answer 11

• Perturbations in this while step lead to a new reality of the defects that come from defective and neurotic closure
• For e.g. Craniorachischisis. Consists in the complete opening of the neural tube
• This means the first stage of closing doesn’t occur appropriately and the structure remains open

Question 12

What is it called when the neural tube opening remains only in the anterior portion?

Answer 12

Anencephalic

Question 13

What is it called when the opening remains in the caudal most region of the neural crest?

Answer 13

Spina bifida

Question 14

Where does neural closure occur in mice?

Answer 14

• In 3 different places
• Closure 1: located at the end between the hind brain and the spinal cord
• Closure 2: located at the edge between the forebrain and the midbrain (starts a bit later than closure 1)
• Closure 3: Located in the most rostral portion of the forebrain (starts a bit later than closure 2), only progresses posteriorly due to being rostral

Question 15

Where does neural closure occur in humans?

Answer 15

• Humans have the same closure points as mice but has 2 more closure points in addition
• Closure 4: Occurs more rostral with the hind brain compared to closure 1
• Closure 5: Located in the very posterior portion of the neural plate and progressing on the anterior

Question 16

What are the 2 modes of the neural plate closure?

Answer 16

• Primary neurulation
• Secondary neurulation

Question 17

What occurs in primary neurulation?

Answer 17

• Rolling up of the tube
• Closure is by fold apposition then “zipping up”
• Finally is at the cranial and caudal neuropores

Question 18

What occurs during secondary neurulation?

Answer 18

• Tunnelling or hollowing of the tail bud
• Occurs at the most caudal region of the neural tube

Question 19

What is the relationship between the primary and secondary neurulation?

Answer 19

• The primary and secondary neural tube becomes continuous
• They fuse with each other
• Located at the region of somites 30-32 in humans

Question 20

Briefly describe primary neuralation
What are the 2 main processes that are essential for the efficient folding of the neural tube in primary neuralation?

Answer 20

• Shaling of the neural plate occurs by convergence/extension (1)
• Tubing requires bending at hinge points
• Cell wedging at hinge points: Microtubules and actin filaments (2)

Question 21

What are these processes controlled by from a molecular point of view?

Answer 21

Controlled by the planer cell polarity pathway

Question 22

Describe the process of convergence-extension (VD)

Answer 22

• A process of lengthening by narrowing, which requires cells to become polarised, in the plane of the cell layer
• They then intercalate amongst eachother
• The structure changes the formation from a broad short tissue to a long narrow tissue (Occurs during the shaping of the neural plate)

Question 23

What is this process controlled by?
What does it contain?

Answer 23

• Controlled by the wind planer solitary pathway
• Otherwise known Wnt-PCP pathway
• Wnts: Secreted signalling molecules: the ligand
• Frizzleds: Wnt receptor, transmembrane proteins
• Vangl and Celsr: Co-receptors necessary for signal transduction
• Dvl1-3: Cytoplasmic proteins, activated upon interaction between Wnts and Fzds

Question 24

13:00