Brain Development

Question 1

What is primary and secondary neurulation

Answer 1

Primary: Edges of the neural plate fold up to form a tube

Secondary: The tub hollows out

Question 2

What are the 3 primary vesicles and the 5 secondary vesicles in A/P axis segmentation

Answer 2

3:
- Forebrain
- Midbrain
- Hindbrain

5:
- Telencephalon
- Diencephalon
- Mesencephalon
- Metencephalon
- Myelencephalon

Question 3

Outline the process of regional patterning of the nervous system?

(include what it is, the french flag model, and the morphogens involved)

Answer 3

• RP is the process that divides the neuroectoderm into areas that will lay the basis for regional specialisation of a structure in the mature NS
• It is achieved through giving cells their positional information
• This is done via the FFM (group of cells called organiser release morphogen etc)
  In neurulation, morphogens are released from the floor plate and roof plate (motor neurons ventral, commissural neurons dorsal)
• Two key morphogens are BMP (roof) and SHH (floorplate) of the SC (studied in chick embryos)
• These pattern the DV axis
• SHH controls the progenitor domain-specific expression of several homeodomain tfs
• Organisers help control AP patterning, lying at the boundry between two segments (e.g., isthmic organiser between midbrain and hindbrain releases FGF8 forming tectum and cerebellum)

Question 4

There are two classes of T.Fs that SHH impacts, what’s the difference between them?

Answer 4

Class I tfs are repressed by SHH
Class II tfs are induced by SHH

Question 5

Describe the development of the cerebral cortex and describe why human CCs are bigger than murine CCs

Answer 5

• CC required for all higher brain function
• rate of apoptosis and rate of neuron production influence brain size,
• Rate of neuron production is determined by: Length of neurogenic period and by characteristics of progenitor cells
• Pasko Rakic developed the radial unit hypothesis: cerebral cortex develops as and array of cortical columns originating from radial glia cells (found through GFP staining + progeny tracking)
• Apical radial glia cells (and basal progenitors) are the main progenitor cells in murine development. They can undergo symmetric (form two radial glia cells) or asymmetric division
• Two types of asymmetric division; Direct neurogenesis - RG form one neuron and one stem cell
  Indirect neurogenesis - RG forms basal progenitor + a stem cell (which can further subdivide into 2 neurons)
• In humans, the outer subventricular zone is massively enlarged and contains many more radial glia. These OUTER radial glia can divide much quicker than apical radial glia - increased density

Question 6

Why is it important to study brain development?

Answer 6

Offers insights into its functioning not easily achievable from analysis of the adult brain

Neural progenitor cells follow predictable stages of proliferation, differentiation, migration and maturation, but the mechanisms controlling the progression through each stage are incompletely understood

Characterising and treating neurodevelopmental disorders

Injury repair processes are similar to those that occur in development

Question 7

What are conditions that can arise from too much / too little neuronal proliferation

Answer 7

macrocephaly / microcephaly