Limb development Flashcards
What are the 3 axis ?
Anterior-posterior
distal-proximal
dorsal-ventral
What direction is anterior to posterior ?
up to down
What direction is distal to proximal?
left to right
What direction is dorsal to ventral?
front to back
Where is the origin of the initial growth?
flank of mesoderm
What signal is key in the initial growth?
FGF
What does FGF initiate?
Initiates signal transduction cascade to target genes.
TF of Tbx family
Outgrowth using Tbx induced by fibreglass growth factor
What does FGF stand for?
Fibroblast Growth factor
What is flank?
Side of body mesoderm
What is the AER ?
Apical Ectodermal Ridge
What does the AER express?
FGF genes and FGF proteins
What is the AER derived from?
ectoderm derived structures
What does FGF travel through?
Mesenchyme
What does FGF bind to?
FGF binds to receptor signals
What role does AER play in initiating growth? X4
Important signalling centre
maintains outgrowth
produces FGF
controls proximal to distal
Is the AER like a ‘seem’?
YES.
Does AER pattern or differentiate cells?
Pattern
In what zone can cells detect FGF?
Progressive zone
How is identity created in these cells?
time spent in progressive zone
might be counted by cell divisions
What axis is the initial growth on?
Proximal to distal
What two molecule signal opposing gradients?
FGF and RA
What kind of gradient does 2-signal model have?
opposing
antagonism between them
What happens to intermediate areas in 2-signal model?
may adopt intermediate fates
What axis is FGF present?
AXIAL
What axis is RA present?
Proximal
What does FGF promote?
proliferation
What does RA promote?
differentiation
How does FGF inhibit RA?
Inhibits Raldh2, this will limit RA
How does RA inhibit FGF?
inhibits Fgf8 transcription, promotes transcription degradation
How do cells know what signal to follow? FGF or RA?
Depends on how close or how strong each signal is.
If a signal appears first it will dominate.
How is patterning achieved across anterior to posterior axis?
ZPA (polarising region)
What gene does ZPA have?
morphogen
what specific signal is produced from ZPA?
Sonic Hedgehog signals
What does a high concentration of sonic hedgehog signal induce at (proximal region)?
induce a pinky to form
What digit number is a pinky?
5 (in humans)
Does Posterior or Anterior have the highest concentration of sonic hedgehog signal?
Posterior
can you create a ZPA on opposing anterior side?
YES= opposing gradients
How does strength of opposing signal from ZPA effect duplication?
weak signal = very little mirror image duplication
What is preaxial polydactyly?
Extra anterior digit due to loss of shh= loss of ZPA
How is the mutant shh regulated ?
cis-regulation 1,000,000 bp away
What patterns the dorso-ventral axis?
ectoderm
What is a way to describe the mesenchyme?
meaty bit
What patterns the mesenchyme?
ectoderm, compartmentalise to dorsal and ventral side
What gene (TF) confers dorsal fate?
Lmx1b
What ligand (extracellular signalling molecule) induces Lmx1b?
Wnt7a
Where is Wnt7a produced?
ectoderm
Where does Wnt7a diffuse to?
mesenchyme and induces expression of Lmx1b
What receptor activation activities Transcription factor En1?
BMP
What gene (TF) confers Ventral fate?
En1
What does ligand does En1 repress?
Wnt7a and in turn represses Lmx1b
Can both pathways ventral and dorsal pathways occurs at the same time?
No
What ligand signals for cell death?
BMP
What tissue determines cell death?
mesoderm
What are HOX genes?
tell cell if they are going to be an arm, leg etc. Tell cells their location from anterior to posterior on entire embryo.
What 3 molecules initiate the initial bud development?
Hox gene, Wnts and FGF in flank
What 2 regions in turn help maintain each other?
apical ectodermal ridge and the polarising region (in limb bud)
