The AER cells then begin to express FGF8 themselves. If radical fringe is expressed ectopically elsewhere in the limb bud, another AER will form on the border of expressing and non-expressing cells. Generation of the axes of the limb Proximal-Distal Axis 1. Development of the elements is sequential starting proximally. This was established by experiments in the 1940's in which the AER was removed from an early stage limb bud.
Elongation ceases and only the humerus develops.
AER does not determine the stage of limb development an AER from a late stage embryo can be grafted onto the mesoderm of an early embryo, and the limb will develop normally. The PZ is required for growth of the limb. The AER and PZ reciprocally promote each other. And, persistence of the AER depends on a maintenance factor from the mesenchyme. The FGFs mentioned earlier are the main players in these interactions.