The most primitive skeletal pattern consists of ribs projecting from vertebrae, from the head through to the tail. In mice, ribs are restricted to the thoracic region, and the axial skeleton consists of seven cervical, 13 thoracic, six lumbar, four sacral, and a variable number of caudal vertebrae. Hox genes control the patterning of the skeleton, but exactly how they achieve this has been confused by the redundant function of genes within the four chromosomal linkage groups, A–D, which arose during evolution by genomic duplication events. In the July 18 Science, Deneen M. Wellick and Mario R. Capecchi at the Howard Hughes Medical Institute clarify our understanding of skeletal development by knocking out each redundant copy in two of 13 paralogous sets of Hox genes. This reveals that these genes interact with one another in repressing the basic primitive skeletal pattern (Science, 301:363-367, July 18, 2003).


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