Apical ectodermal ridge

The apical ectodermal ridge (AER) is a critical component in vertebrate limb development. The AER is an ectodermal structure overlying and inducing the developing limb bud of the vertebrate embryo, and will eventually give rise to the skin covering the limb. Initial formation of the AER is induced by secretion of the fibroblast growth factor FGF-10 from the somatic layer of the lateral plate mesoderm. This initial induction is believed to result from the activity of Hox genes. The AER then secretes FGF-8 back into the mesoderm, stimulating its proliferation and the formation of the progress zone. Continued secretion of FGF-8 by the AER sustains limb formation throughout the process of development.

The AER also signals to the Zone of Polarizing Activity (ZPA), which establishes the anterior-posterior axis (thumb versus pinky finger) in the limb bud.

AER manipulation experiments

If for any reason the AER is removed or inactivated during development of limb, proliferation in the progress zone will cease resulting in limb truncation and agenesis of distal structures. Transplantation of an AER to another area of mesoderm will only result in formation of an additional limb if the underlying mesoderm has already been induced to give rise to a limb. If the AER is transplanted adjacent to another AER, supernumary structures will result: an additional limb forms as a mirror image next to the already developing limb. The mirror image reflection is a result of the transplanted AER obeying signals from the existing ZPA.

Transplantation of an AER that would give rise to an arm (or wing, as these experiments are commonly performed on chicken embryos) to a limb field developing into a leg does not produce an arm and leg at the same location, but rather two legs. In contrast, transplantation of cells from the progress zone of a developing arm to replace the progress zone of a developing leg will produce a limb with leg structures proximally (femur, knee) and arm structures distally (hand, fingers). Thus it is the mesodermal cells of the progress zone, not the ectodermal cells of the AER, that control the identity of the limb. The development of the proximal-distal axis is controlled by the amount of time cells spend in the progress zone and the expression of Hox genes.

Implantation of a plastic bead soaked in FGF-8 will induce formation of a limb bud in an embryo, but proliferation will cease prematurely unless additional beads are added to maintain appropriate levels of FGF-8. Implantation of sufficient beads can induce formation of a 'normal' additional limb at an arbitrary location in the embryo.

A bead of FGF10 implanted in tissue functions like the AER.