Tissue Repair 1 - Building the Mammalian Midbrain

Question 1

Explain the anterior (rostral) - posterior (caudal) axis

Answer 1

• anterior (rostral) - front of brain
• posterior (caudal) - the back (by the neck)

Question 2

What does the metencephalon differentiate into?

Answer 2

hindbrain

Question 3

What does the mesencephalon differentiate into?

Answer 3

midbrain

Question 4

What do the diencephalon and telencephalon differentiate into?

Answer 4

forebrain

Question 5

What is the dorsal and ventral axis of the neural tube?

Answer 5

Doral - roof plate
ventral - floor plate

Question 6

Where do dorsal root ganglion neurone form?

Answer 6

Dorsal end of neural tube

Question 7

Where do motor neurone form?

Answer 7

the floor plate of the spinal chord

Question 8

What secrets SHH in midbrain development?

Answer 8

• notochord
• floor plate

Question 9

What does SHH activate in mid brain development?

Answer 9

Gli TF

Question 10

Explain the signal transduction of SHH in midbrain development

Answer 10

• binds to receptor PTCH1
• PTCH1 stops repressing SMO receptor
• SMO activates Gli pathway
• Gli activates target genes

Question 11

Explain Gli distribution across the neural tube

Answer 11

• gradient which is strongest at the floor plate, mimics SHH distribution

Question 12

What do different strengths of Gli activation lead to?

Answer 12

• different neurons along the neural tube

Question 13

Give 2 TFs that Gli and therefore SHH activates in mid brain development and explain their activation thresholds

Answer 13

• Nkx6.1 - Low Gli threshold
• Nkx2.2 - High Gli threshold

Question 14

Explain the activation threshold of Olig2 in midbrain development

Answer 14

• only active at mid concentrations
• feedback loops

Question 15

Explain the possible combinations of gene activation in mid-brain development

Answer 15

• negative feedback - Expression of the gene active at high concentrations can inhibit transcription of other genes
• Interactions with other transcriptional activators and repressors

Question 16

Explain the expression of FOXA2

Answer 16

• turned on by SHH only in the floor plate of the midbrain

Question 17

What is the role of tyrosine hydroxylase?

Answer 17

an enzyme needed to make dopamine

Question 18

Explain the expression of Lmx1a

Answer 18

• restricted to the floor plate and is expressed in DA neurons

Question 19

Explain the expression of Msx1/2

Answer 19

• restricted to the floor plate and not in DA neurone

Question 20

Explain the transcription of Lmx1a, Msx1/2 and Nurr1 in midbrain development

Answer 20

• As cells leave the floor plate they stop expressing Msx1/2 and continue expressing Lmx1a
• as they leave they start expressing tyrosine hydroxylase
• Nur1 is not expressed in floor plate. It is expressed once cells leave the floor plate

Question 21

Explain the expression of Nurr1

Answer 21

• expressed in DA neurons and not in the floor plate

Question 22

Where is Nkx61 expressed in the mid brain?

Answer 22

• not in the floor plate or DA neurons

Question 23

Where is Pax7 expressed in midbrain development?

Answer 23

• near roof plate

Question 24

What will happen if you take lateral tissue from the neural tube and culture it?

Answer 24

• it will default to Doral tissue (roof plate)

Question 25

What will happen if you take lateral tissue from the neural tube and culture it with SHH?

Answer 25

• It will default to ventral tissue (floor plate)
• TFs specific to midbrain tissue will only be expressed in tissue that came from the midbrain

Question 26

What is the isthmic organiser?

Answer 26

• between midbrain and hindbrain
• express FGF8 gradient in each direction
• anterior posterior organiser

Question 27

Explain the Wnt gradient across the neural tube

Answer 27

• highest at posterior
• lowest at anterior

Question 28

Give an overview of midbrain patterning

Answer 28

• High SHH signalling instructs ventral tissue
• FGF8 + medium Wnt signalling instructs midbrain tissue
• FGF8 + high Wnt signalling instructs hindbrain tissue