SOX9 BINDS DNA, ACTIVATES TRANSCRIPTION, AND COEXPRESSES WITH TYPE-IICOLLAGEN DURING CHONDROGENESIS IN THE MOUSE

Two lines of evidence suggest that the Sry-related gene Sox9 is import ant for chondrogenesis in mammalian embryos. Sox9 mRNA is expressed in chondrogenic condensations in mice, and mutations in human SOX9 are k nown to cause skeletal dysplasia. We show here that mouse SOX9 protein is able to bind to a SOX/SRY consensus motif in DNA and contains a mo dular transcriptional activation domain, consistent with a role for SO X9 as a transcription factor acting on genes involved in cartilage dev elopment. One such gene is Col2a1, which encodes type II collagen, the major structural component of cartilage. We have compared, in detail, the expression of Sox9 and Col2a1 during mouse development. In chondr ogenic tissues the expression profiles of the two genes were remarkabl y similar. Coexpression was detected in some nonchondrogenic tissues s uch as the notochord, otic vesicle, and neural tube, but others such a s heart and lung differed in their expression of the two genes. Immuno histochemistry using an antibody specific for SOX9 revealed that expre ssion of SOX9 protein mirrored the distribution of Sox9 mRNA. Our resu lts suggest that SOX9 protein is involved in the regulation of Col2a1 during chondrogenesis, but that this regulation is likely to depend on additional cofactors. (C) 1997 Academic Press.