In insects, segmental identity is specified by the homeotic genes, which in Drosophila are found in two separate clusters (ANT-C and BX-C) and in the beetle Tribolium in a single one (HOM-C). These genes contain a conserved DNA sequence, the homeobox, which encodes a 60 amino acid DNA-binding region. Recent work on the mouse has resulted in the identification of four clusters of homeobox containing genes, the Hox genes, which appear to be true homologues of the insect ANT-C plus BX-c, with the same spatial organization along the chromosome and showing the same relative order of expression along the anterior- posterior axis. Similar clusters have been found in other vertebrates, including humans. While the function of the vertebrae genes is mostly unknown, the structural homologies of the Hox and HOM clusters have led to the proposal that an ancestral version of these gene clusters arose before the protostome-deuterostome evolutionary divergence and that it was involved in the specification of positional information during development. Dr. Macagno proposes to characterize the corresponding cluster (LOX-C) of these genes in a more primitive invertebrate, the leech and to compare it to the insect and mammalian clusters in terms of structure, expression and organization, He has already identified several leech homeobox genes which are expressed in spatiotemporal patterns resembling those of vertebrate Hox and insect homeotic genes. %%% This investigation will contribute to our understanding of the evolution and function of a set of genes important in morphogenesis.
