PARALLEL EXPRESSION OF SOX9 AND COL2A1 IN CELLS UNDERGOING CHONDROGENESIS

To assess the role of the transcription factor Sox9 in cartilage forma tion we have compared the expression pattern of Sox9 and Col2 alpha 1 at various stages of mouse embryonic development, Expression of Col2 a lpha 1 colocalized with expression of Sox9 in all chondroprogenitor ce lls. In the sclerotomal compartment of somites the onset of Sox9 expre ssion preceded that of Col2 alpha 1. A perfect correlation was also se en between high levels of Sox9 expression and high levels of Col2 alph a 1 expression in chondrocytic cells. However, no Sox9 expression was detected in hypertrophic chondrocytes; only low levels of Col2 alpha 1 RNA were found in the upper hypertrophic zone, Coexpression of Sox9 a nd Col2 alpha 1 was also seen in the notochord. At E11.5 Sox9 expressi on in the brain and spinal neural tube was more widespread than that o f Col2 alpha 1 although at E14.5 Sox9 and Col2 alpha 1 transcripts wer e colocalized in discrete areas of the brain. Distinct differences bet ween Sox9 and Col2 alpha 1 expression were observed in the otic vesicl e at E11.5. At E8.5, expression of Sox9 but not of Col2 alpha 1 was se en in the dorsal tips of the neural folds and after neural tube closur e also in presumptive crest cells emigrating from the dorsal pole of t he neural tube. No Col2 alpha 1 expression was detected in gonadal rid ges in which high levels of Sox9 expression were detected. Together wi th our previous results showing that the chondrocyte-specific enhancer element of the Col2 alpha 1 gene is a direct target for Sox9, these r esults suggest that Sox9 plays a major role in expression of Col2 alph a 1. The correlation between high expression levels of Sox9 and high e xpression levels of Col2 alpha 1 in chondrocytes suggests the hypothes is that high levels of Sox9 are needed for full expression of the chon drocyte phenotype; lower levels of Sox9 such as in neuronal tissues wh ich are also associated with lower expression levels of Col2 alpha 1 w ould be compatible with other cell specifications. (C) 1997 Wiley-Liss , Inc.