Chondrocytes as a specific target of ectopic Fos expression in early development.
The Finkel-Biskis-Jinkins murine sarcoma virus, which carries v-fos, induces osteosarcomas, whereas high-level expression of exogenous c-fos in transgenic and chimeric mice leads to postnatal development of osteogenic and chondrogenic tumors, respectively. To test whether such target cell specificity of an oncogene can be detected even in early development, 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 proliferating chondrocytes into mature or hypertrophic chondrocytes, as well as a slight delay in precartilagenous condensation. Expression of 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 macroscopic abnormalities in limb formation, indicating a specific function of Fos proteins in embryonic endochondral bone differentiation. The extent of truncation was stronger with v-Fos than with c-Fos, and comparative analysis of these proteins, as well as v-Fos mutants, revealed that strong transforming activity of Fos protein is necessary to cause dysplasia, suggesting that common molecular mechanisms are involved in both embryonic chondrodysplasia and bone tumor formation in postnatal mice.
Watanabe
H
H
Department of Gene Regulation, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Saitoh
K
K
Kameda
T
T
Murakami
M
M
Niikura
Y
Y
Okazaki
S
S
Morishita
Y
Y
Mori
S
S
Yokouchi
Y
Y
Kuroiwa
A
A
Iba
H
H
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics*; D002356:Cartilage / Q000196:embryology; D002642:Chick Embryo; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D005822:Genetic Vectors; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics*; D011247:Pregnancy; D012190:Retroviridae