SOX9 Binds DNA, Activates Transcription, and Coexpresses with Type II Collagen during Chondrogenesis in the Mouse

Two lines of evidence suggest that theSry-related geneSox9is important for chondrogenesis in mammalian embryos.Sox9mRNA is expressed in chondrogenic condensations in mice, and mutations in humanSOX9are known 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 modular transcriptional activation domain, consistent with a role for SOX9 as a transcription factor acting on genes involved in cartilage development. One such gene isCol2a1,which encodes type II collagen, the major structural component of cartilage. We have compared, in detail, the expression ofSox9andCol2a1during mouse development. In chondrogenic tissues the expression profiles of the two genes were remarkably similar. Coexpression was detected in some nonchondrogenic tissues such as the notochord, otic vesicle, and neural tube, but others such as heart and lung differed in their expression of the two genes. Immunohistochemistry using an antibody specific for SOX9 revealed that expression of SOX9 protein mirrored the distribution ofSox9mRNA. Our results suggest that SOX9 protein is involved in the regulation ofCol2a1during chondrogenesis, but that this regulation is likely to depend on additional cofactors.