The role of Hox genes in limb development.

In order to directly test the function of Hox genes in vertebrate limb development, we have employed a replication-competent retroviral vector to express the genes ectopically in developing chick limb buds. It has been hypothesized that the sum of all Hox genes expressed in a developing region forms a "Hox code" which determines the fate of structures arising from that region. When the Hox code of the of the anlage of the chicken hind limb digit I is altered to match that of digit II, the resulting foot has two similar toes both resembling digit II in morphology. This suggests that the misexpressed gene, Hox-4.6, plays a role in controlling digit morphological identity. Other phenotypes observed in the proximal parts of the hind limb and in similar experiments in the wing also lend support to this interpretation. The retroviral vector system used in these experiments provides a powerful approach for testing the function of genes in limb development.