Joint formation begins during embryogenesis, when stripes of high cell density called interzones form across developing skeletal precursors (Haines 1947). Programmed cell death occurs within the interzone, and a three-layered interzone forms that has two layers of higher cell density flanking a region of lower cell density. Non-joint precursors of the skeleton typically develop into cartilage, which hypertrophies and is replaced by bone. However, cells within the high-density layers of the interzone are excluded from this process and develop into the permanent layers of articular cartilage found in the mature joint (Mitrovic 1978).