Chapter 3

Question 1

what is induction? what is compentence?

Answer 1

induction: close range interaction of different types of cells

competence: ability to respond to specific inductive signal

Question 2

what is Hans Spemann do?

Answer 2

transplanted frog gastrula ectoderm cells into newt gastrula
- they ended up switching mouths
- proved that induction tells them what to do, but not how to do it (genes encode for that)

Question 3

what is juxtacrine signaling? what are three examples

Answer 3

direct contact b/w the inducing & responding cells
- delta-notch, cadherins, integral MB ligands

Question 4

what are cadherins?

Answer 4

calcium dependent, transmembrane integral protein that attaches to a cytoskeleton

cells that are the most sticky (more surface tension) are in the middle

creates a hierarchy of cell types based on surface tension

Question 5

endocrine vs paracrine?

Answer 5

endocrine: hormones via bloodstream, long-distance

paracrine: short-distance, diffuses into ECM

Question 6

what are morphogens?

Answer 6

a type of inducing paracrine that creates cell pattern & form

Question 7

describe how paracrines form a gradient

Answer 7

little to no paracrine signal = no response
medium signal = response #1
large signal = response #7

• cells nearby get a large dose, those further away get a small dose and produce a different response

Question 8

what are the four families of paracrines?

Answer 8

FGF (fibroblast growth factor)
hh (hedgehog)
Wnt (wingless)
TGF-beta (transforming growth factor)

Question 9

what does FGF do?

Answer 9

development & tissue maintenance
- makes limbs grow longer

Question 10

what does hedgehog do?

Answer 10

orientates cells in relation to other cells
- anterior (pinky) & posterior (thumb)
- dependent on a gradient of HH signal

Question 11

what does Wnt do?

Answer 11

establishes polarity
- communicates which cells get FGF & hedgehog

Question 12

what does TGF-beta do?

Answer 12

regulates ECM
- differentiation b/w cell types

Question 13

describe the general way signal transduction works?

Answer 13

paracrine binds and induces activation of proteins

Question 14

what type of paracrine uses RTK? (receptor tyrosine kinases)

Answer 14

FGF (fibroblast growth factor)

Question 15

describe the RTK pathway

Answer 15

1. ligand / paracrine binds RTK receptor
2. receptor dimerizes
3. autophosphorylation of receptor & tyrosine residues
4. adaptor protein
5. GNRP
6. Ras becomes active –> RasGTP
7. Raf
8. MEK
9. ERK, enters nucleus
10. TFs activate (Mift)
11. transcription occurs

Question 16

describe the canonical Wnt pathway

Answer 16

1. Wnt (ligand) binds to frizzled protein (receptor)
2. disheveled
3. blocks GSK-3 inhibitor
4. frees beta-catenin & it accumulates (no phosphorylation)
5. goes inside nucleus & binds to LEF/TCF
6. transcription occurs

Question 17

what is ubiquitin and how does it relate to the canonical Wnt pathway?

Answer 17

ubiquitin
- tag put on cells to be degraded by the proteasome

• phosphorylation of beta-catenin by GSK-3 causes ubiquitin to bind
• causes beta-catenin to be degraded

Question 18

what are the layers in the ECM (extracellular matrix) and how does it regulate paracrines?

Answer 18

epithelium, basal lamina, collagen

fibronectin = long, EXM molecule, “road”

integrins = span from ECM to intracellular matrix
- integrate things from ECM (signal carried inside from outside)

Question 19

what is anoikis and how does this ECM function regulate paracrines?

Answer 19

death upon detachment from ECM
- occurs if integrin detaches from fibronectin matrix, it can no longer function

Question 20

what is the function of Bcl-2 & Bcl-XL?

Answer 20

they inhibit apoptosis when activated

Question 21

how can Bcl-2 & Bcl-XL start apoptosis? what is the pathway?

Answer 21

must be inhibited by Bik or Bax
- active Bik/Bax inhibits Bcl-2
- activates Apaf 1
- caspase-9 cleaves off inhibitory region of caspase-3 to initiate apoptosis

Question 22

what happens to apoptosis if the alternative splice site of Bcl, Bcl-XS, is activated?

Answer 22

it is unable to inhibit Apaf 1, so apoptosis occurs

Question 23

what are caspases?

Answer 23

starts off as a zymogen (what it’s called before activation) that has an inhibitory region
- once the inhibitory region is cleaved, the caspase is activated

RELEASE THE BEAST

Question 24

what is meant by maintaining differentiation?

Answer 24

I am a muscle cells, now I need to stay a muscle cell

Question 25

what are the four ways cells can maintain differentiation?

Answer 25

1. autoregulation via TFs
2. promoter stabilization
3. autoregulation via autocrine signaling loop
4. paracrine signaling loop

Question 26

describe autoregulation via TFs

Answer 26

the gene gets activated & produces a TF that activates the gene again
- all occurs intracellularly, TFs bind to two different enhancers on the same gene

Question 27

describe promoter stabilization

Answer 27

protein binds to promoter (ex: trithorax) & prevents nucleosome formation so it is always active, always unwound

Question 28

describe autoregulation via autocrine signaling loop

Answer 28

gene releases a ligand molecule that binds to it’s own receptor outside cell
- receptor keep activating the gene, which causes the release of another ligand that the gene is activated by

Question 29

describe paracrine signaling loop

Answer 29

two nearby cells exchange & make ligands for each other to keep each other active

Question 30

what are two stages of commitment to a cell type? describe them

Answer 30

1. specification = receives signal
   - when removed, it will still differentiate, but new signals can change fate
2. determination = starts to do signal, maintenance processes start
   - new signals cannot change fate