Lecture 5- Basic Mechanisms

Question 1

in cell regulation, what are intrinsic factors?

Answer 1

Transcription factors than either increase or decrease transcription - come from inside of cell

Question 2

does 1 trascription factor regulate one gene?

Answer 2

no- often goes on to regulate several genes

Question 3

what are extrinsic factors?

Answer 3

signals coming from outside the cell

ligands than bind and activate a receptor, causing a conformational change in a second messenger/ signal cascade

Question 4

in early development how many cell fates are there?

Answer 4

4

Question 5

what are these 4 cell fates?

Answer 5

endoderm, ectoderm, neuroectoderm and mesoderm

Question 6

what controls which of the 4 cell fates is formed?

Answer 6

a morphegen (extrinsic factor) which interacts with receptors to give a second messenger and affect a master TF

Question 7

what happens if an embryonic stem cell goes long enough without being induced?

Answer 7

it will follow it’s pre-determined path- so will become neuroectoderm

Question 8

what does each of the 4 pathways need to do to secure their cell fate is formed?

Answer 8

increase a master TF above a particular threshold.

Question 9

what 2 factors determine whether or not TF threshold is overcome?

Answer 9

• morphogen concentration (higher conc.= quicker decison)

- length of time exposed to morphogen (low dose can have a cummulative effect over prolonged time)

Question 10

what are the 4 main morphogen pathways?

Answer 10

• TGF1 (transposing growth factor pathway)
• BMP4 (bone morphogenetic pathway)
• WNT pathway
• FGF pathway

Question 11

what pathway does TGF1 take stem cells?

Answer 11

endoderm/endomesoderm/ mesoderm

Question 12

what pathway does BMP4 take stem cells?

Answer 12

ectoderm

Question 13

what pathway does WNT take stem cells?

Answer 13

mesoderm

Question 14

what pathway does FGF take stem cells?

Answer 14

neuroectoderm

Question 15

is FGF required to give neuroectoderm?

Answer 15

probably not as it’s the pre-determined cell fate

Question 16

what MTF genes are needed to be upregulated to give neuroectoderm?

Answer 16

OCT4 and SOX2

Question 17

what happens once the 4 main cell type pathways have done their work and main cell types have matured?

Answer 17

the cells go on to switch on new gradients

Question 18

what is competence?

Answer 18

switching on other gradients in an area where it was previously absent

Question 19

what is digital function?

Answer 19

where there’s a TF threshold above which genes are activated to drive the cell down a different fate pathway (e.g cell A or cell B)

Question 20

what’s analogue function?

Answer 20

where high, intermediate and low affinity genes are activated to give different cell substrates (e.g. Cell Ba, Cell Bb or Cell Bc)

Question 21

in an analogue function, what will low TF concentrations bind to?

Answer 21

only genes with a high affinity

Question 22

in an analogue function, what will high TF concentrations bind to?

Answer 22

activate additional genes. Those with the highest affinity, 2nd highest and so on… (allows a single TF to give multiple cell fates)

Question 23

what happens at border/ centre cells (cells between 2 cell types which haven’t recieved a high enough TF conc. to become cells on either side?

Answer 23

these are Naive cells which can be instructed to make different cell types

Question 24

what are the 2 possible outcomes of border/centre (naive cells)?

Answer 24

they may be influenced bu the newly committed cells on either side
or
the unique boundary cells will now generate and secrete a new gradient signal that subpatterns them

Question 25

which 2 additional signaling pathways are critical for neural tube patterning?

Answer 25

• Sonic Hedgehog (SHH)

- Retanoic Acid (RA)

Question 26

do SHH and RA generate analogue or digital sub-fate?

Answer 26

analogue

Question 27

are SHH and RA intrinsic or extrinsic factors?

Answer 27

extrinsic

Question 28

what does SHH bind?

Answer 28

transmembrane receptor

Question 29

what does RA bind?

Answer 29

nuclear receptor

Question 30

what is SHH key for?

Answer 30

ventral patterning of neural tube

Question 31

what’s RA key for?

Answer 31

rhombomere patterning of hindbrain