Vertebrate gene members of the HoxD complex are essential for proper d
evelopment of the appendicular skeletons, Inactivation of these genes
induces severe alterations in the size and number of bony elements, Ev
x-2, a gene related to the Drosophila even-skipped (eve) gene, is loca
ted close to Hoxd-13 and is expressed in limbs like the neighbouring H
erd genes. To investigate whether this tight linkage reflects a functi
onal similarity, we produced a null allele of Evx-2. Furthermore, and
because Hoxd-13 function is prevalent over that of nearby Herd genes,
we generated two different double mutant loci wherein both Evx-2 and H
oxd-13 were inactivated in cis, The analysis of these various genetic
configurations revealed the important function of Evx-2 during the dev
elopment of the autopod as well as its genetic interaction with Hoxd-1
3, These results show that, in limbs, Evx-2 functions like a Herd gene
, A potential evolutionary scenario is discussed, in which Evx-2 was r
ecruited by the HoxD complex in conjunction with the emergence of digi
ts in an ancestral tetrapod.