RECIPROCAL CHANGES IN HOX D13 AND RAR-BETA-2 EXPRESSION IN RESPONSE TO RETINOIC ACID IN CHICK LIMB BUDS

The finding that retinoic acid (RA) has major effects on pattern forma tion in developing chick limbs has led to the conclusion that RA plays a central role in the normal development of the limb. In addition, it has been demonstrated that treatment with exogenous RA leads to chang es in expression of homeobox-containing Hox complex genes within the d eveloping limb. This has been used to argue that, since RA activates 5 ' Hox D complex genes in the same temporal and spatial sequence as in normal development, Hox genes might be regulated by RA during normal l imb development. In this study, we further examine the temporal and sp atial changes in expression of Hox D13 and RAR-beta 2 transcripts in w ing buds in response to local application of RA in vivo. We confirm re ports that RAR-beta 2 expression is induced early and locally by RA. H owever, we find that the effect of RA on Hox D13 gene expression at th e distal end of wing buds at stage 25/26 is downregulation of transcri pt expression. Furthermore, we find that activation of ectopic Hox D13 expression in response to implantation of RA beads along the anterior margin at stage 20/21 is indirect. Finally, the effects of RA exposur e on Hox D13 expression appear to directly correlate with effects on t he pattern of distal skeletal elements. (C) 1994 Academic Press, Inc.