2nd year recap

Question 1

What is neurogenesis?

Answer 1

The growth and development of the nervous tissue

Question 2

When does neural patterning and neurogenesis occur?

When is this process in humans?

Answer 2

After the formation of the neural tube from the neural plate

Between 4-12 weeks

Question 3

How does the neural plate roll up to become the neural tube?

At what somite stage?

Answer 3

NOT uniform:

• First to roll up becomes the HINDBRAIN
• Lots of morphogenesis

0-3 somite stage

Question 4

What is spinal bifida?

Answer 4

When the spinal cord doesn’t close

Question 5

Where is the neural tube wider? Why?

Answer 5

At the BRAIN - due to more cell proliferation

Question 6

What breaks the symmetry of the neural tube?

Answer 6

Differential proliferation (more are the brain)

Question 7

How do neurons form?

What is this governed by?

What does this determine?

Answer 7

Same as cell differentiation in any part of the body:

• Cells become DIFFERENT from each other and ACQUIRE SPECIALISED properties
• Governed by CHANGES in GENE EXPRESSION, which dictate the REPERTOIRE of protein synthesised
• REPERTOIRE of proteins translated dictate a cells BEHAVIOUR (eg. proliferation, migration etc)

Question 8

How do CHANGES in GENE EXPRESSION dictate the REPERTOIRE of protein synthesised?

Answer 8

Determine which proteins are transcribed and translated into protein and determine which proteins are actively repressed

Question 9

What happens to the potency of a cell over time? Why?

Answer 9

Potency is REDUCED - cells become more specialised/differentiated as repertoire of protein changes

Question 10

What 2 things are gene expression (repertoire of proteins/genes) in a cell governed by?

Answer 10

1) EXTRINSIC factors (morphogens and signals)

2) INTRINSIC factors (transcription factors)

Question 11

When does differentiation occur?

Answer 11

Over TIME as CELLS DIVIDE

Question 12

What cells are neurons born from?

Answer 12

Progenitor cells

Question 13

What are progenitor cells?

Answer 13

Cells that are slightly more specialised than stem cells but aren’t fully committed (have lost some potency)

Tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its “target” cell

Question 14

Where is the action of TF important?

Answer 14

In progenitor cells

Question 15

As progression of a cell occurs, what does the cell become dependant on?

Answer 15

TF (switch from morphogens)

Question 16

What causes the differentiation of neurons?

Answer 16

Secreted morphogens and intrinsic transcription factors

Question 17

What does ISH of shh mRNA in the neural tube show?

Answer 17

Shh is NOT INITIALLY expressed in the neural tube itself

1) INITIALLY expressed in a rod of mesoderm that lies beneath the ventral midline of the neural tube
2) Then shh is expressed in a triangular shaped region at the ventral midline (floor plate)

Question 18

What does shh code for?

Answer 18

A SECRETED protein

Question 19

What experimental procedure allows to see protein?

Answer 19

Antibody labelling experiment (make antibody against the protein)

Question 20

What does an antibody labelling experiment of shh show?

Answer 20

• Shh expressed in the notochord and floor plate and in cells next to the floor plate (extending dorsally)

Shows shh:
- Is secreted from cells making it and extends dorsally

Question 21

What type of molecule does shh act as?

What does this do?

Answer 21

Acts as a MORPHOGEN

To induce different progenitor cells along the dorso-ventral axis of the future spinal cord

Question 22

What is a morphogen?

Answer 22

A SECRETED protein which establishes a CONCENTRATION GRADIENT

Question 23

How do cells respond to a morphogen gradient?

Answer 23

Cells respond DIFFERENT THRESHOLDS of morphogen and respond DIFFERENTLY by eliciting DIFFERENT programmes of GENE EXPRESSION - make cells different

Question 24

What is the difference between a stem cell and a progenitor cell?

Answer 24

PC only has a LIMITED NUMBER of cell divisions that it can make before it eventually differentiates

Question 25

How does a progenitor cell become a certain type of neuron?

Answer 25

Due to the TF profile elicited at an earlier point in time

Question 26

What does high concentrations of shh do?

Answer 26

REPRESSES cell cycle genes - limiting cell divisions

Question 27

What are the readouts of shh along the DV axis of the neural tube?

Answer 27

5 BANDS of progenitor domains expressing specific TFs

Question 28

When do cells along the DV axis of the neural tube begin to be different to each other?

Answer 28

When the express different TF as a result of shh gradient

Question 29

Describe ‘cellular memory’

Answer 29

As progenitor divides - daughters know who they are

Question 30

What do TF ‘code’?

Answer 30

Later differentiation:

• Different character of the cells depending on what cell they came from

Question 31

How do progenitors divide?

What do the daughters become?

Answer 31

With asymmetry:
- Daughters stay close to the LUMEN as a PROGENITOR

• Other daughter migrates LATERALLY outwards to build up the radial dimension (width)

Question 32

How are neurons arranged along the DV axis of the neural tube?

What determines what neurons?

Answer 32

Different classes of neurons arranged with bilateral symmetry:

• Motor ventrally
• Middle - different classes of relay neurons
• Anterior - commissural relay neurons

Determined by the progenitor they came from and which TF were expressed in the progenitor cell, determined by the threshold of shh the cells see

Question 33

Why is the top of the neural tube thinner than the ventral?

Answer 33

Due to shh effects on the cell cycle????

Question 34

What molecule sets up the progenitor domains at the dorsal of the neural tube?

Answer 34

BMP/Wnts

Question 35

Ultimately, how many progenitor domains line the neural tube?

Answer 35

10 (5 - shh, 5 BMP/Wnts)

Question 36

Why do axons project to different places as progenitors differentiate?

What are these determined by?

Answer 36

Different axons have different receptors which are determined by the TF the progenitors express

Question 37

Why do commissural axons migrate to the floor plate but motor axons don’t?

Answer 37

Motor axons don’t have netrin receptors but commissural axons do

Question 38

How are neuronal circuits formed?

Answer 38

Function as neurotransmitters cross synapses

Question 39

What is the NT expressed by a cell a feature of?

Answer 39

The TF expressed by the grandmother cell