The posterior HoxA and HoxD genes are essential in appendicular development. 
Studies have demonstrated that a "distal limb enhancer," remotely located 
upstream of the HoxD complex, is required to drive embryonic autopod expression 
of the posterior Hox genes as well as the two additional non-Hox genes in the 
region: Evx2 and Lnp. Our work demonstrates a similar mode of regulation for 
Hoxa13 and four upstream genes: Evx1, Hibadh, Tax1bp, and Jaz1. These genes all 
show embryonic (E11.5-E13.5) distal limb and genital bud expression, suggesting 
the existence of a nearby enhancer influencing the expression of a domain of 
genes. Comparative sequence analysis between homologous human and mouse genomic 
sequence upstream of Hoxa13 revealed a remote 2.25-kb conserved noncoding 
sequence (mmA13CNS) within the fourth intron of the Hibadh gene. mmA13CNS shares 
a common 131-bp core identity within a conserved noncoding sequence upstream of 
Hoxd13, which is located within the previously identified distal limb enhancer 
critical region. To test the function of this conserved sequence, we created 
mmA13CNS-Hsp86-lacZ transgenic mice. mmA13CNS directed a wide range of tissue 
expression, including the central nervous system, developing olfactory tissue, 
limb, and genital bud. Limb and genital bud expression directed by mmA13CNS is 
not identical to the patterns exhibited by Hoxa13/Evx1/Hibadh/Tax1bp1/Jaz1, 
suggesting that mmA13CNS is not sufficient to fully recapitulate their 
expression in those tissues. The Evx1- and Evx2-like central nervous system 
expression observed in these mice suggests that the long-range regulatory 
element(s) for the Hox cluster existed before the cluster duplication.