The joint gene

The formation of joints during foetal development is essential for determining the final skeletal pattern and is also strongly implicated in a number of joint diseases. At present little is known about the complicated molecular mechanisms involved in joint formation, however. In the 9 February issue of Cell, researchers from the Department of Genetics, Harvard Medical School, suggest that Wnt-14 is essential in the initial steps of joint formation.

Christine Hartmann and Clifford Tabin studied the early joint-forming regions of the developing chick limb. They found that Wnt-14 shows a striking pattern of expression in the regions of joint formation. Observations of localized Wnt-14 misexpression indicated that cells within prechondrogenic regions respond to exogenous Wnt-14 and become morphologically and histologically distinct from neighbouring cartilage, taking on histological and molecular properties typical of the early joint interzone (Cell 2001, 104:341-351).

But ectopic Wnt-14 expression led to a repression of joint formation in adjacent cartilage. This provides a potential mechanism for spacing the joints, in which each newly formed joint would block formation of additional joints in its immediate vicinity.