DIFFERENTIAL EXPRESSION OF THE 2 CLOSELY-RELATED LIM-CLASS HOMEOBOX GENES LH-2A AND LH-2B DURING LIMB DEVELOPMENT

We have isolated the chicken homeobox genes LH-2A and LB-2B encoding t wo related LIM domain-containing homeodomain proteins and examined the expression pattern during chick limb development. LH-2A is most close ly related to human and rat LH-2, while LH-2B is less conserved. Altho ugh both LH-2A and LH-2B are expressed in the limb mesenchyme througho ut stage 16 to stage 32, LH-2A transcripts are detectable in the dista l limb bud and LH-2B transcripts are detectable in the anterior limb b ud. Signals from the apical ectodermal ridge positively regulate LH-2A expression, since removal of the apical ectoderm resulted in the rapi d reduction of LH-2A expression in the distal limb mesenchyme. Ectopic expression of the sonic hedgehog gene in the anterior margin of the l imb bud resulted in the rapid reduction of LH-2B expression accompanyi ng respecification of the positional value to the posterior phenotype. These results suggest that LH-2A and LH-2B play important roles in th e determination and specification of the proximal-distal and anterior- posterior positional values, respectively. (C) 1997 Academic Press.