MISEXPRESSION OF HOXA-13 INDUCES CARTILAGE HOMEOTIC TRANSFORMATION AND CHANGES CELL ADHESIVENESS IN CHICK LIMB BUDS

During chick limb development, the Abd-B subfamily of genes in the Hox A cluster are expressed in a region-specific manner along the proximod istal axis. To elucidate the function of Hoxa-13 that is expressed in the autopod during normal limb development, Hoxa-13 was misexpressed i n the entire limb bud with a replication-competent retroviral system. Misexpression of Hoxa-13 resulted in a remarkable size reduction of th e zeugopodal cartilages as a result of the arrest of cartilage eel gro wth and differentiation restricted in the zeugopod. This size reductio n seems to be attributable to homeotic transformation of the cartilage s in the zeugopod to the more distal cartilage, that of the carpus/tar sus. This transformation was specific to Hoxa-13 and was not observed by overexpression of other Hox genes. These results indicate that Hoxa -13 is responsible for switching the genetic code from long bone forma tion to short bone formation during normal development. When the limb mesenchymal cells were dissociated and cultured in vitro, Hoxa-13-expr essing limb mesenchymal cells reassociated and were sorted out from no nexpressing cells. Forced expression of Hoxa-13 at the stage that endo genous Hoxa-13 was not expressed as of yet altered the hemophilic cell adhesive property. These findings indicate the involvement of Hoxa-13 in determining hemophilic cell-to-cell adhesiveness that is supposed to be crucial for the cartilage pattern formation.