It is interesting that the SOX9 transcription factor continues to be expressed in mutant cartilage despite loss of Col2a1, a direct target of this transcription factor (Bell et al. 1997; Lefebvre et al. 1997). Previous studies suggest that SOX9 activity can be modified by protein kinase A (PKA)-dependent protein phosphorylation, or by coexpression of two related proteins, L-SOX5 and SOX6 (Lefebvre et al. 1998; Huang et al. 2000). In addition, close examination of the order of genes induced during chicken digit formation reveals that Sox9 turns on first, followed by Bmpr1b with L-Sox5, and then Sox6 and the cartilage matrix structural components Col2a1 and Agg (Chimal-Monroy et al. 2003). These results, together with the altered pattern of gene expression seen in our Bmpr1a-deficient mice, suggest that BMPR1A signaling may normally act to stimulate SOX9 by post-translational protein modification, or to induce L-Sox5 or Sox6 in cartilage to maintain expression of ECM components. These models are consistent with the ability of BMP2 to both increase PKA activity and induce expression of Sox6 in tissue culture cells (Lee and Chuong 1997; Fernandez-Lloris et al. 2003). Although we have tried to monitor the expression of L-Sox5 or Sox6 in postnatal articular cartilage, and test the phosphorylation state of SOX9 using previously described reagents (Lefebvre et al. 1998; Huang et al. 2000), we have been unable to obtain specific signal at the late postnatal stages required (unpublished data). Furthermore, null mutations in L-Sox5 or Sox-6 cause lethality at or soon after birth, and no effect on cartilage maintenance has been reported (Smits et al. 2001). However, it seems likely that these or other processes regulated by BMP signaling cooperate with SOX9 to induce target genes in articular cartilage.