Apical Ectodermal Ridge - Roles

Roles

• Maintain the limb mesenchyme in a mitotically active state and focused on its task – the distal outgrowth of the limb. This is achieved by secretion of FGF8, which signals the limb mesodermal cells to continue proliferation, and secreting FGF10, which winds up maintaining the AER.

• Sustain expression of the molecules that establish the anterior-posterior axis. The FGFs secreted by the AER act upon the mesenchyme cells – including the zone of polarizing activity (ZPA). Thus, the AER causes the ZPA to continue secreting Sonic hedgehog (Shh), which is involved with Hox gene expression in establishing the anterior-posterior polarity in the developing limb. Shh also activates Gremlin, which inhibits bone morphogenetic proteins (BMPs) that would normally block FGF expression in the AER. In this manner, the ZPA and AER sustain each other through a positive feedback loop involving FGFs, Shh, and Gremlin.

• Communicate with the proteins that determine the anterior-posterior and dorsal-ventral axes to supply instructions concerning differentiation and cell fates. The FGFs secreted by the AER interact with the limb mesenchyme – including the ZPA – to induce further FGF and Shh expression. These signals then regulate Hox gene expression, which influence differentiation activity and determines what phenotypes the cells will adopt. The secreted Shh also activates Gremlin, which inhibits members of the BMP family. BMPs inhibit FGF expression in the AER, so the FGF secreted by the AER ends up providing feedback (via Shh and Gremlin) that will dictate cellular differentiation involved in sculpting the limb.