CNS and Brain Development

Question 1

In specification of the dorsoventral axis, where do sensory and motor neurons sit?

Answer 1

Sensory neurons go into the dorsal spinal cord.

Motor neurons sit ventrally.

Question 2

What is the Sonic Hedgehog morphogen secreted by?

Answer 2

The notochord

Question 3

What is secretion of Shh by the notochord required for?

Answer 3

Development of midline structures

Question 4

What is highly conserved in the notochord?

Answer 4

Expression of Shh

Question 5

What does the expression of Shh in the notochord determine?

Answer 5

Cell fate as you move from ventral to dorsal through the neural tube

Question 6

Give the reading on specification of the dorso-ventral axis.

Answer 6

Engrailed gene is also thought to play a role in dorsoventral patterning.
Limbs of mice lacking Engrailed showed a double-dorsal phenotype.
Engrailed acts to define ventral ectodermal identity.

Question 7

In which species was Shh first identified?

Answer 7

Drosophila melanogaster

Question 8

Dissected neural tube was cultured in different concentrations of Shh.
How did this impact neuronal identity?

Answer 8

High concentrations of Shh - became almost all motor neurons.

With anti-Shh to block Shh action - no neuronal cells were produced.

Question 9

What are the two roles of Shh in CNS and brain development?

Answer 9

• Specification of the dorso-ventral axis

- Neuronal identity

Question 10

Give the reading for Shh and neuronal identity.

Answer 10

• Progenitor cells either Nkx2.2 or Pax6 in response to graded Shh signalling,
• Mice lacking Pax6, progenitor cells generated neurons characteristic of high Shh activity.
• Pax6 controls neuronal pattern indirectly.

Question 11

What do different combinations of transcription factors define?

Answer 11

Progenitor cell populations in the ventral neural tube

Question 12

When different transcription factors are overlaid, what does this create?

Answer 12

Different types of neurons

Question 13

How does Sox2 function?

Answer 13

To maintain neural progenitor identity.

Question 14

Give the extra reading for transcriptional definition of progenitor domains.

Answer 14

• SOX2 functions to maintain neural progenitor identity.
• Expression of SOX2 inhibits neuronal differentiation and results in maintenance of progenitor characteristics.
• Inhibition results in onset of early neuronal differentiation markers.

Question 15

What are Robo and Slit essential for?

Answer 15

The formation of commissures

Question 16

Why do bodies need a sense of left and right side from commissures?

Answer 16

For sensory processing and locomotion

Question 17

What animal is used to understand commissure formation?

How?

Answer 17

Drosophila

Nerves stained with antibodies

Question 18

Explain how Robo and Slit lead to the formation of commissures.

Answer 18

• Axon expressing Robo is repelled by Slit and grows longitudinally
• Robo is down-regulated, and the axon is no longer sensitive to Slit at the midline
• The axon crosses over
• Robo is up-regulated, and the axon remains on the colateral side.

Question 19

What happens in Robo mutants?

Answer 19

Axons cross and recross at the midline because they are insensitive to Slit

Question 20

What happens in Slit mutants?

Answer 20

Axon tracts collapse to the midline of the body and only respond to attractive signals