Keeping up with the zone of polarizing activity: New roles for an old signaling center

The vertebrate limb is an excellent model organ system to investigate how signaling pathways interact. Over the last half-century, experiments investigating patterning in the vertebrate limb have led directly to the discovery of many of the molecules and molecular pathways that are not only responsible for limb patterning but the patterning of many different organ systems. In the limb bud, the zone of polarizing activity (ZPA) has long been known to produce factor(s) that are essential for normal limb formation. Recently, one of these factors, Sonic Hedgehog (SHH) was shown to function not only in the limb bud mesenchyme but also in the ectoderm overlying the ZPA. This review discusses the role and potential implications hedgehog signaling in the limb bud ectoderm plays in patterning the vertebrate limb.