Limb Development and Disrupting Embryonic Development Flashcards
Each of the following limb development regions is responsible for which part?
a. Stylopod
b. Zeugopod
c. Autopod
a. Humerus
b. Ulna and radius
c. Carpals and digits
What are the critical regions in the developing limb bud?
Progress zone, zone of polarizing activity (ZPA), apical ectodermal ridge (AER)
Where is the ZPA located?
Posterior mesenchyme of the limb bud
Where is the AER located?
At the boundary of dorsal and ventral sides of the limb bud
AER is required for patterning which axes of the limb bud?
Proximal-distal, dorsal-ventral, anterior-posterior
What can replace the AER activity?
Implantation of FGF bead
RA concentration is higher on the __________ axis and Fgf/Wnt concentration is higher on the ___________ axis
Proximal; distal
Which genes are linked to the stylopod, zeugopod and autopod?
Meis for stylopod, Hox11 for zeugopod and Hox13 for autopod
What is RA responsible for in limb bud PD patterning?
RA activates Meis genes and promotes proximal formation of the limb bud
What is FGF/Wnt responsible for in limb bud PD patterning?
FGF initiates Hox13 genes and promotes distal formation of the limb bud
Hoxa11/Hoxd11-deficient mice are missing which limb part?
Zeugopod
In humans, homozygous mutation in Hoxd13 causes which disorder?
Polysyndactyly (fused digits)
What does AER activity require?
Limb bud mesenchyme
PD specification of the limb is correlated with what factor?
The age of the progress zone mesenchyme
___________ and ___________ is expressed in dorsal ectoderm, ___________ is expressed in ventral ectoderm
Wnt7a; Lmx1; En-1
A loss of Lmx1 causes what effect?
Ventralized dorsal side, causing two ventral sides
Knockout of Engrailed causes what effect on the limb?
Loss of ventral patterning
Addition of AER tissue to the forelimb mesenchyme causes what effect?
Digit duplication
ZPA transplantation of mouse ZPA to chick causes what effect?
Formation of digits
What is expressed in ZPA?`
Shh
Transplanting ZPA of Shh beads causes what effect?
Mirror image duplication
Identify the response to Shh signaling to the digits
a. Shh independent
b. Differentiation dependent on Shh concentration (paracrine)
c. Shh-dependent; time-dependent (autocrine)
a. Digit 1
b. Digits 2 and 3
c. Digits 4 and 5
(Fgf8/Shh) is expressed in the ZPA after (Fgf8/Shh) is expressed in the AER
Shh; Fgf8
What is the mechanism of FGF activating Shh with the activity of Grem1?
Grem1 stimulates FGF when FGF is low
High FGF stimulates Shh expression and represses Grem1 activity
Low Grem1 activity decreases FGF expression