Proximal to distal patterning during limb development and regeneration: a review of converging disciplines

Regeneration of lost structures typically involves distinct events: wound healing at the damaged site, the accumulation of cells that will be used as future building blocks and, finally, the initiation of molecular signaling pathways that dictate the form and pattern of the regenerated structures. Amphibians and urodeles in particular, have long been known to have exceptional regenerative properties. For many years, these animals have been the model of choice for understanding limb regeneration, a complex process that involves reconstructing skin, muscle, bone, connective tissue and nerves into a functional 3D structure. It appears that this process of rebuilding an adult limb has many similarities with how the limb forms in the first place--for example, in the embryo, all the components of the limb need to be formed and this requires signaling mechanisms to specify the final pattern. Thus, both limb formation and limb regeneration are likely to employ the same molecular pathways. Given the available tools of molecular biology and genetics, this is an exciting time for both fields to share findings and make significant progress in understanding more about the events that dictate embryonic limb pattern and control limb regeneration. This article focuses particularly on what is known about the molecular control of patterning along the proximal-distal axis.