TOWARD UNDERSTANDING SOX9 FUNCTION IN CHONDROCYTE DIFFERENTIATION

The transcription factors that trigger the determinative switch to cho ndrocyte differentiation in mesenchymal cells are still unknown. In hu mans, mutations in the gene for SOX9, a transcription factor with a DN A-binding domain similar to that of the mammalian testis-determining f actor SRY, cause campomelic dysplasia, a severe dwarfism syndrome whic h affects all cartilage-derived structures. During mouse embryonic dev elopment, the Sox9 gene becomes active in all prechondrocytic mesenchy mal condensations, and at later stages its expression is maintained at high levels in fully differentiated chondrocytes. A chondrocyte-speci fic enhancer in the gene for collagen type II (Co/2a1), a characterist ic marker of chondrocytes, is a direct target for SOX9, and ectopic ex pression of SOX9 in transgenic mouse embryos is sufficient to activate the endogenous Co/2a1 gene in some tissues. These data suggest that S OX9 could have a major role in chondrogenesis. Studies are in progress to identify other target genes for SOX9 in chondrocytes and also othe r transcription factors that are believed to cooperate with SOX9 in th e activation of chondrocyte-specific genes. Defining SOX9 function and the mechanisms that regulate SOX9 gene expression should contribute t o a better understanding of chondrocyte differentiation.