Articular cartilage has a fundamental role in joint function. While much is known about its structure, organization and biomechanical properties, there is a very poor understanding of how articular chondrocytes develop during embryogenesis and acquire the unique ability to organize and maintain the articular tissue. Given that articular cartilage forms in close juxtaposition with the joint, here we review past studies on limb joint determination and morphogenesis and more recent studies on a number of factors thought to have roles in joint and epiphysis development. These factors include: the homeobox gene Barx-1; the bone morphogenetic protein (BMP) family member GDF-5; the growth factors HGF and PTHrP; and the transcription factor ERG. We summarize current thinking on how these factors participate in joint development and how some of these factors may influence development and behavior of epiphyseal chondrocytes. We also describe pertinent recent studies from our laboratories on ERG and the newly-identified alternatively spliced variant C-1 - 1, and finally propose a sequela of events that may subtend the process of determination and emergence of articular chondrocytes during limb synovial joint development.
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