Differential expression of chicken CYP26 in anterior versus posterior limbbud in response to retinoic acid

Multiple studies indicate that quantitative control of the levels of all-tr ans-retinoic acid (RA) in the vertebrate embryo is necessary for correct de velopment. The function of RA in cells is regulated by a number of coordina ted mechanisms. One of those mechanisms involves controls on the rate of RA catabolism. Recently, enzymes capable of catabolizing RA were found to con stitute a new family, called CYP26, within the cytochrome P450 superfamily. CYP26 homologues have been isolated from human, mouse, zebra fish, and rec ently from the chick. In this study, we examined the regulation of chicken CYP26 (cCYP26) expression by RA during the early phase of chick limb outgro wth. In the anterior limb mesenchyme and apical ectodermal ridge (AER), cCY P26 expression was induced in a concentration dependent manner by implantin g beads soaked in 0.1, 1, and 5 mg/ml RA. The RA-induced expression of cCYP 26 in anterior limb mesenchyme and the AER was detected as early as 1 hr af ter treatment and was not affected by the presence of cycloheximide. In con trast to the anterior limb, the induction of cCYP26 was dramatically reduce d (or absent) when RA beads were implanted in the posterior limb mesenchyme . Furthermore, induction of cCYP26 expression in the anterior mesenchyme wa s inhibited by transplantations of the zone of polarizing activity (ZPA) an d by Shh-soaked beads. Our data suggest that different mechanisms regulate retinoid homeostasis in the AER and mesenchyme during limb bud outgrowth. ( C) 2001 Wiley-Liss, Inc.