Fingers and toes

The mammalian Hox gene clusters display remarkable 'quantitative colinearity' — not only does the temporal and spatial expression during development reflect the order of genes on the chromosome, but genes at the 5' end of the cluster are expressed at the highest levels. In the November 14 Nature, Marie Kmita and colleagues analyze a series of deletion mutations within the mouse Hoxd locus designed to investigate the mechanisms underlying colinearity in limbs (Nature, 420: 145-150, November 14, 2002).

Deletion and duplications of the Hoxd13, Hoxd12 and Hox11 genes were generated using targeted meiotic recombination (TAMERE) technology. Disruption or deletion of the Hoxd13 gene resulted in very different digit phenotypes and deletion also affected the expression of neighboring genes. The location within the gene cluster was critical and Hoxd genes were functionally upregulated when shifted to replace the equivalent position of upstream neighbors. Duplications of Hoxd genes and their promoter regions ...