THE MURINE HOXC CLUSTER CONTAINS 5 NEIGHBORING ABDB-RELATED HOX GENES THAT SHOW UNIQUE SPATIALLY COORDINATED EXPRESSION IN POSTERIOR EMBRYONIC SUBREGIONS

A common feature of the murine Abdominal B (AbdB)-related Hox genes, located in the 5' regions of the four Hox clusters, appears to be a function in patterning the developing limb. As a prerequisite for studying the role of the AbdB-related Hoxc genes during limb development, we have isolated and mapped the three predicted AbdB-related Hoxc-11, -12, and -13 loci, thus defining the 5' end of the Hoxc cluster. Sequence comparisons based on the homeobox sequences of presumably all murine AbdB-related Hox genes strongly support the concept of a two step process in their evolution. As expected, Hoxc-11, -12 and -13 exhibit nested and extremely posteriorly restricted expression domains, whose anterior boundaries reflect their map positions, in accordance with the colinearity rule. A limited comparison of the primary expression domains of all five AbdB-related Hoxc genes in the developing hindlimb revealed nested and increasingly restricted domains of expression in the mesenchyme for only Hoxc-9, -10 and -11. However, separate localized expression was detected for Hoxc-9, -10, -11, -12 and possibly -13 in distal epidermal regions of the developing hind- and forelimb, whereas no expression of any of the five genes was observed in mesenchymal tissues of the developing forelimb. These data suggest a specific role for the AbdB-related Hoxc genes in patterning the hindlimb and pelvic girdle, which is separate from a second role relevant for both hind- and forelimb development.