l4

Question 1

how does hypothalamus produce anterior progenitors?

Answer 1

combines proliferation signal (Fgf) with differentiating signal (Shh)

(self sustaining system due to proliferation - large supply of anterior progenitors which can differentiate into different types of hypothalamic neuron)

Question 2

how does Shh act in the spinal cord to select different prognitors?

Answer 2

• acts as a spatial morphogen
• concentration gradient acts to generate different types of neurons in the sc (cells differentiate differently to different concentrations of Shh due to different thresholds)

Question 3

in the spinal cord what do ventral neurons differentiate in response to?

Answer 3

• have a high Shh threshold - ventral most neurons differentiate in response to very high concentrations of Shh (V3 - motor neurons)
• intermediate neurons differentiate at lower concenrations of Shh (V0,1,2)

Question 4

what happens in cells in the absence of shh/ligand?

Answer 4

• Smo is prevented from reaching the cilia membrane as it is supressed by Ptc (on cell surface)
• GliR

Question 5

what happens in a cell when there is the prescence of Shh/ligand?

Answer 5

Shh binds to ptc-1 - endocytosed +degraded

- Smo is therefore derepressed and can reach the cilia membrane - GliA

Question 6

what are the co-receptors/TMRs which can also bind to Shh?

Answer 6

• gas1
• Boc
• cdo

Question 7

what are cdo and gas1 required for?

Answer 7

cdo and gas1 are required for Shh to bind to ptc - and so that Smo can become activated

Question 8

what happens if there is no gas1/cdo/boc?

Answer 8

• there is no activation of smo
  (even if Shh if bound to Ptc)
• loss of ventral pattern induced by Shh in sc

Question 9

when are coreceptors to prc downregulated (cdo/boc/gas1)

Answer 9

cdo/gas1/boc are downregulated when there is Shh signalling

- negative feedback

Question 10

how is ligand dependant anatgonism achieved?

Answer 10

by a combination of cell autonomous and cell non-autonomous negative feedback mechansims

Question 11

what does ligand dependent antagonism of Shh signalling do?

Answer 11

• limits the spread of Shh (more local activation)
• steapens the gradient of Shh
• downregulates Shh in more distal areas from the source
• decrease sensitivities of cells

Question 12

give the cell autonomous LDA mechanism

Answer 12

transcriptional feedback loops control the level of Shh receptors present on the cell surface

Question 13

give the cell non-autonomous LDA mechanism

Answer 13

increase in receptors that bind Shh limit the spread of Shh itself

Question 14

what is upregulated during Shh signalling?

Answer 14

Hhip, ptc1 and ptc 2 receptors

• bind to Hh ligands so compete with productive ligand -receptor complexes
• alter balance between bound + unbound Ptc
• limits Shh spread due to sequestration (non-autonomous)