Alternative transcript of the chick alpha 2(I) collagen gene is transiently expressed during endochondral bone...

Endochondral bone formation is characterized by several transitions in the pattern of collagen gene expression, the best characterized of which occurs during chondrogenesis. Prechondrogenic mesenchymal cells synthesize predominantly type I collagen; during chondrogenesis, type I collagen synthesis ceases and production of cartilage-characteristic collagens is initiated. We previously identified the molecular mechanism that mediates cessation of alpha 2(I) collagen synthesis in chondrocytes (Bennett and Adams [1990] J. Biol. Chem. 265:2223-2230). This mechanism involves a change in the transcription initiation site, resulting in an alternative transcript that cannot encode alpha 2(I) collagen. In this report we demonstrate that the alternative transcript appears only transiently in cartilage. Its initial appearance is coincident with the onset of high levels of type II collagen synthesis in differentiated chondrocytes. However, it disappears in hypertrophic cartilage, and production of the authentic alpha 2(I) collagen mRNA is reinitiated, contributing to synthesis of a high level of type I collagen in hypertrophic chondrocytes at the chondro-osseous junction. We also show that the alternative transcript is not restricted to cartilage during embryonic development, since it initially appears in presomite embryos, well before the appearance of cartilage. At early stages of embryo-genesis the alternative transcript is restricted to tissues derived from neuroectoderm; its appearance in those tissues is also transient. These data suggest that production of the alternative transcript of the alpha 2(I) collagen gene may be required for cessation of alpha 2(I) collagen synthesis during chondrogenesis, but the alternative transcript may be involved in other important developmental programs as well.