Limb development

Question 1

What are the 3 axis ?

Answer 1

Anterior-posterior
distal-proximal
dorsal-ventral

Question 2

What direction is anterior to posterior ?

Answer 2

up to down

Question 3

What direction is distal to proximal?

Answer 3

left to right

Question 4

What direction is dorsal to ventral?

Answer 4

front to back

Question 5

Where is the origin of the initial growth?

Answer 5

flank of mesoderm

Question 6

What signal is key in the initial growth?

Answer 6

FGF

Question 7

What does FGF initiate?

Answer 7

Initiates signal transduction cascade to target genes.
TF of Tbx family
Outgrowth using Tbx induced by fibreglass growth factor

Question 8

What does FGF stand for?

Answer 8

Fibroblast Growth factor

Question 9

What is flank?

Answer 9

Side of body mesoderm

Question 10

What is the AER ?

Answer 10

Apical Ectodermal Ridge

Question 11

What does the AER express?

Answer 11

FGF genes and FGF proteins

Question 12

What is the AER derived from?

Answer 12

ectoderm derived structures

Question 13

What does FGF travel through?

Answer 13

Mesenchyme

Question 14

What does FGF bind to?

Answer 14

FGF binds to receptor signals

Question 15

What role does AER play in initiating growth? X4

Answer 15

Important signalling centre
maintains outgrowth
produces FGF
controls proximal to distal

Question 16

Is the AER like a ‘seem’?

Answer 16

YES.

Question 17

Does AER pattern or differentiate cells?

Answer 17

Pattern

Question 18

In what zone can cells detect FGF?

Answer 18

Progressive zone

Question 19

How is identity created in these cells?

Answer 19

time spent in progressive zone

might be counted by cell divisions

Question 20

What axis is the initial growth on?

Answer 20

Proximal to distal

Question 21

What two molecule signal opposing gradients?

Answer 21

FGF and RA

Question 22

What kind of gradient does 2-signal model have?

Answer 22

opposing

antagonism between them

Question 23

What happens to intermediate areas in 2-signal model?

Answer 23

may adopt intermediate fates

Question 24

What axis is FGF present?

Answer 24

AXIAL

Question 25

What axis is RA present?

Answer 25

Proximal

Question 26

What does FGF promote?

Answer 26

proliferation

Question 27

What does RA promote?

Answer 27

differentiation

Question 28

How does FGF inhibit RA?

Answer 28

Inhibits Raldh2, this will limit RA

Question 29

How does RA inhibit FGF?

Answer 29

inhibits Fgf8 transcription, promotes transcription degradation

Question 30

How do cells know what signal to follow? FGF or RA?

Answer 30

Depends on how close or how strong each signal is. | If a signal appears first it will dominate.

Question 31

How is patterning achieved across anterior to posterior axis?

Answer 31

ZPA (polarising region)

Question 32

What gene does ZPA have?

Answer 32

morphogen

Question 33

what specific signal is produced from ZPA?

Answer 33

Sonic Hedgehog signals

Question 34

What does a high concentration of sonic hedgehog signal induce at (proximal region)?

Answer 34

induce a pinky to form

Question 35

What digit number is a pinky?

Answer 35

5 (in humans)

Question 36

Does Posterior or Anterior have the highest concentration of sonic hedgehog signal?

Answer 36

Posterior

Question 37

can you create a ZPA on opposing anterior side?

Answer 37

YES= opposing gradients

Question 38

How does strength of opposing signal from ZPA effect duplication?

Answer 38

weak signal = very little mirror image duplication

Question 39

What is preaxial polydactyly?

Answer 39

Extra anterior digit due to loss of shh= loss of ZPA

Question 40

How is the mutant shh regulated ?

Answer 40

cis-regulation 1,000,000 bp away

Question 41

What patterns the dorso-ventral axis?

Answer 41

ectoderm

Question 42

What is a way to describe the mesenchyme?

Answer 42

meaty bit

Question 43

What patterns the mesenchyme?

Answer 43

ectoderm, compartmentalise to dorsal and ventral side

Question 44

What gene (TF) confers dorsal fate?

Answer 44

Lmx1b

Question 45

What ligand (extracellular signalling molecule) induces Lmx1b?

Answer 45

Wnt7a

Question 46

Where is Wnt7a produced?

Answer 46

ectoderm

Question 47

Where does Wnt7a diffuse to?

Answer 47

mesenchyme and induces expression of Lmx1b

Question 48

What receptor activation activities Transcription factor En1?

Answer 48

BMP

Question 49

What gene (TF) confers Ventral fate?

Answer 49

En1

Question 50

What does ligand does En1 repress?

Answer 50

Wnt7a and in turn represses Lmx1b

Question 51

Can both pathways ventral and dorsal pathways occurs at the same time?

Answer 51

No

Question 52

What ligand signals for cell death?

Answer 52

BMP

Question 53

What tissue determines cell death?

Answer 53

mesoderm

Question 54

What are HOX genes?

Answer 54

tell cell if they are going to be an arm, leg etc. Tell cells their location from anterior to posterior on entire embryo.

Question 55

What 3 molecules initiate the initial bud development?

Answer 55

Hox gene, Wnts and FGF in flank

Question 56

What 2 regions in turn help maintain each other?

Answer 56

apical ectodermal ridge and the polarising region (in limb bud)