L16 - Development of Neurotransmitters

Question 1

Where does the dorsal spinal cord come from?

Answer 1

Zygote - blastocyst - post-implantation epiblast
Patterning along anterior- posterior axis caused by gradients of proteins
- Retinoic acid and FGF

Question 2

Afferents from the DRG will target different laminae

Answer 2

Pain/thermos - laminae I, II
Touch - laminae IIinner – V
Proprioception - laminae III-V

Question 3

Anterior-posterior regionalisation

Answer 3

Each region expresses specific transcription factors
Transcription factors specify different neural cell types that emerge at particular
- Positions
- Developmental stages

Question 4

Dorsal-ventral patterning - graded signals

Answer 4

BMP, WNT - roof plate

SHH – floor plate

Question 5

Progenitors in ventricular zone respond to?

Answer 5

BMP, WNT and SHH
They segregate into zones
Migrate laterally and generate the neuronal sub-types
Different transcription factor combinations define sub-types
- Class A - relay interneurons
- Class B - association interneurons

Question 6

Evidence that BMPs are involved in dorsal progenitor formation

Answer 6

E.g. Loss of GDF7 - leads to loss of D1A but not D1B neurons
E.g. Roof plate removed by expressing Diptheria toxin
- At E11 - loose dorsal progenitors

Question 7

Evidence that WNTs are involved in dorsal progenitor formation - enhanced WNT signalling

Answer 7

Dorsal genes expressed more ventrally

Question 8

Evidence that WNTs are involved in dorsal progenitor formation - reduced WNT signalling

Answer 8

Ventral genes expressed more dorsally

Question 9

Ablation ectopic expressions experiments with WNT suggest?

Answer 9

Neurons still produced from domains

Fate altered

Question 10

Signalling gradients induce transcription factors

Answer 10

SHH gradient induces transcription factors

BMPs and WNT pattern dorsal cell identity

Question 11

Cross antagonism refines the pattern set up by transcription factors

Answer 11

dI4 - dI6 neurons

• LBX1 expressed from dI4-dI6
• PAX2 expressed in dI4 (inhibitory)
• TLX3 expressed in dI5 (excitatory)
• TLX3 example of a switch

Question 12

Patterned progenitors to specific neural subtypes

Answer 12

Express different neurotransmitters and different migratory patterns
Therefore different
- Sites or axonal projections
- Circuit integration

Question 13

Neuron migration during spinal cord development

Answer 13

Lineage tracing shows neurons migrate long distances from VZ
- Some dl1 neurons end up in ventral horn (rather than dorsal)
At different rostro-caudal positions these maps will alter

Question 14

Development of diLB neurons is post mitotic

Answer 14

dILB neurons

• Are excitatory
• Settle in the dorsal horn

Question 15

diLB neurons express

Answer 15

E12 - Lbx1, Pou4f1, Tlx3, Lamx1b +ve
E13.5 (dorsal spinal cord) - layered expression
Superficial layer – Tlx3, Lamx1b +ve and Pou4f1, Lbx1 -ve
Ventral layer – Lbx1, Pou4f1 +ve

Question 16

Are neurons inhibitory or excitatory?

Answer 16

Depends on expression of particular transcription factors

• Ptf1a – inhibitory - diLA
• Gsx1/2 – excitatory - diLB

Question 17

How do we get circuits?

Answer 17

eurons of the dorsal hindbrain and spinal cord – receive, process and relay sensory information
- Have to be patterned to make the different neuronal sub-types that build circuits
Transcription factors define neurotransmitter phenotype
Neurotransmitter phenotypes define function
Neurons send axons to connect to targets
Connections established and refined by activity-based pruning

Question 18

How are the neuropeptide and transmitter phenotypes set up in inhibitory neurons?

Answer 18

Involves

• Pax2
• Lhx 1/5
• GABA+
• Neurod 1/2/6

Question 19

To get diLA neurones with dynorphin and galanin?

Answer 19

Pax2 + Neurod 1//2/6

Question 20

To get diLA neurones with NPY and enkephalin?

Answer 20

Pax2 + Lhx1/5