Studies over the last 10 y have begun to elucidate some of the signaling pathways that contribute to the early stages of joint formation. Wnt14 is expressed in stripes at the sites where joints will form, and it is capable of inducing expression of other joint markers when misexpressed at new locations in the limb (Hartmann and Tabin 2001). Several members of the bone morphogenetic protein (BMP) family of secreted signaling molecules are also expressed in stripes at sites where joints will form, including those encoded by the genes Gdf5, Gdf6, Gdf7, Bmp2, and Bmp4 (Storm and Kingsley 1996; Wolfman et al. 1997; Francis-West et al. 1999; Settle et al. 2003). Of these, Gdf5 expression is most strikingly limited to regions where joints will develop and is one of the earliest known markers of joint formation. Mutations in either Gdf5 or the closely related Gdf6 gene also block formation of joints at specific locations, providing strong evidence that these molecules are essential for the joint formation process (Storm et al. 1994; Settle et al. 2003). However, mutations in Bmp2 or Bmp4 cause early embryonic lethality, making it difficult to test their role in joint formation (Winnier et al. 1995; Zhang and Bradley 1996).