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When an extra AER is added, two limbs form. When forelimb mesenchyme is replaced with hindlimb mesenchyme, a hindlimb grows. When forelimb mesenchyme is replaced with non-limb mesenchyme, the AER regresses, and limb development halts. When the AER from a late limb bud is transplanted to an earlier limb bud, the limb forms normally.
The ZPA forms where the Hox8 region joins the AER. These regions are dependent on signaling in order for the appropriate induction events to occur. The AER expresses FGF8 which induces Shh expression in the posterior mesoderm. Shh then stimulates FGF4 to be expressed in the posterior part of the AER. After these events, there is a co-dependence ...
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