ALTERNATIVE TRANSCRIPT OF THE CHICK ALPHA-2(I) COLLAGEN GENE IS TRANSIENTLY EXPRESSED DURING ENDOCHONDRAL BONE-FORMATION AND DURING DEVELOPMENT OF THE CENTRAL-NERVOUS-SYSTEM

Endochondral bone formation is characterized by several transitions in the pattern of collagen gene expression, the best characterized of wh ich occurs during chondrogenesis. Prechondrogenic mesenchymal cells sy nthesize predominantly type I collagen; during chondrogenesis, type I collagen synthesis ceases and production of cartilage-characteristic c ollagens is initiated. We previously identified the molecular mechanis m that mediates cessation of alpha 2(I) collagen synthesis in chondroc ytes (Bennett and Adams [1990] J. Biol. Chem, 265:2223-2230). This mec hanism involves a change in the transcription initiation site, resulti ng in an alternative transcript that cannot encode alpha 2(I) collagen . In this report we demonstrate that the alternative transcript appear s only transiently in cartilage, Its initial appearance is coincident with the onset of high levels of type II collagen synthesis in differe ntiated chondrocytes, However, it disappears in hypertrophic cartilage , and production of the authentic alpha 2(I) collagen mRNA is reinitia ted, contributing to synthesis of a high level of type I collagen in h ypertrophic 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 embryo s, well before the appearance of cartilage, At early stages of embryog enesis the alternative transcript is restricted to tissues derived fro m neuroectoderm; its appearance in those tissues is also transient. Th ese data suggest that production of the alternative transcript of the alpha 2(I) collagen gene may be required for cessation of alpha 2(I) c ollagen synthesis during chondrogenesis, but the alternative transcrip t may be involved in other important developmental programs as well. ( C) 1996 Wiley-Liss, Inc.