Cooperative activation of Chox-4 homeobox genes by factors from the polarizing region and the apical ridge in chick limb morphogenesis.

When a mouse zone of polarizing activity (ZPA) at the posterior margin of the limb bud was grafted at the anterior margin of the chick limb bud, we found that expression of the chick homeobox genes, Chox-4.7 and -4.8, was induced prior to the formation of chick extra digits. The induction was observed in the restricted domain close to both grafted mouse ZPA and the chick apical ectodermal ridge (AER). When the posterior half of the AER was removed, the normal expression was diminished in the posterodistal region. Thus, it is likely that at least two distinct factors, one from the ZPA and the other from the AER, provide positional information to induce cooperatively the sequential expression of the Chox-4 genes.