CHONDROCYTES AS A SPECIFIC TARGET OF ECTOPIC FOS EXPRESSION IN EARLY DEVELOPMENT

The Finkel-Biskis-Jinkins murine sarcoma virus, which carries v-fos, i nduces osteosarcomas, whereas high-level expression of exogenous c-fos in transgenic and chimeric mice leads to postnatal development of ost eogenic and chondrogenic tumors, respectively. To test whether such ta rget cell specificity of an oncogene can be detected even in early dev elopment, we induced ectopic expression of fos in chicken limb buds by microinjecting replication-competent retrovirus into the presumptive leg field of stage 10 embryos. This caused cartilage truncation of all the long bones of the injected leg, which was mainly attributable to chondrodysplasia due to severe retardation of differentiation of the p roliferating chondrocytes into mature or hypertrophic chondrocytes, as well as a slight delay in precartilagenous condensation. Expression o f genes for all the other known members of chicken AP-1, which include such transforming genes as c-jun and fra-2, however, caused no macros copic abnormalities in limb formation, indicating a specific function of Eos proteins in embryonic endochondral bone differentiation. The ex tent of truncation was stronger with v-Fos than with c-Eos, and compar ative analysis of these proteins, as well as v-Fos mutants, revealed t hat strong transforming activity of Eos protein is necessary to cause dysplasia, suggesting that common molecular mechanisms are involved in both embryonic chondrodysplasia and bone tumor formation in postnatal mice.