Expression of Dlx5 and Dlx6 during specification of the elbow joint

The onset of elbow joint formation in the developing limb is characterized morphologically by the conversion of differentiated chondrocytes at the site of incipient joint formation into the densely packed flattened cells of the joint interzone. However, experimental studies have indicated that the elbow joint is specified well before joint interzone formation by a distinctive population of precursor cells located at the site in the developing limb bud at which the elbow joint will subsequently form. Here we show that during specification of the elbow joint in the chick limb bud, the homeodomain transcription factors Dlx5 and Dlx6 are highly expressed by a discrete group of cells that encompass the prospective elbow joint. The Dlx5- and Dlx6-expressing cells at the prospective elbow joint are located where the differentiating humerus branches into the radius and ulna. Thus, Dlx5 and Dlx6 are the earliest molecular markers of the presumptive elbow joint yet described. The onset of Dlx5 expression in the region of the presumptive elbow joint is shortly followed by the initiation of expression amongst the Dlx5-expressing cells of Gdf5, which encodes a secreted signaling molecule that is involved in regulating the onset of joint formation. These results suggest that Dlx genes may be involved in specification of the elbow joint and/or in providing positional information that specifies the site at which the elbow joint will form.