Defining boundaries during joint cavity formation: going out on a limb.

Whilst factors controlling the site at which joints form within the developing limb are recognised, the mechanisms by which articular element separation occurs during the formation of the joint cavity have not been determined. Herein, we review the relationships between early limb patterning, embryonic movement, extracellular matrix composition, local signalling events and the process of joint cavity formation. We speculate that a pivotal event in this process involves the demarcation of signalling boundaries, established by local mechano-dependent modifications in glycosaminoglycan synthesis. In our opinion, studies that examine early patterning and also focus on local developmental alterations in tissue architecture are required in order to help elucidate the fundamental principals regulating joint formation.