Cloning of a novel retinoic-acid metabolizing cytochrome P450, Cyp26B1, and comparative expression analysis with Cyp26A1 during early murine development

Tight regulation of retinoic acid (RA) distribution in the embryo is critic al for normal morphogenesis. The RA-metabolizing enzymes Cyp26A1 and Cyp26B 1 I are believed to play important roles in protecting certain embryonic ti ssues from inappropriate RA signaling. We have cloned the murine Cyp26B1 cD NA and compared its expression pattern to that of Cyp26A1 from embryonic da y (E) E7-E11.5 using in situ hybridization. Northern blot analysis shows th e presence of two Cyp26B1 transcripts of approximately 2.3 and 3.5 kb in em bryonic limb bud. Whereas Cyp26A1 is expressed in gastrulating embryos by E 7, Cyp26B1 is first expressed at E8.0 in prospective rhombomeres 3 and 5. C yp26B1 expression expands to specific dorso-ventral locations in rhombomere s 2-6 between E8.5 and E9.5, whereas Cyp26A1 hindbrain expression is limite d to rhombomere 2 at E8.5. No (or very weak) Cyp26B1 expression is observed in the tail bud, a major site of Cyp26A1 expression. Differential expressi on is seen in branchial arches, with Cyp26A1 being mainly expressed in neur al crest-derived mesenchyme, and Cyp26B1 in specific ectodermal and endoder mal areas. Cyp26B1 is markedly expressed in the ectoderm and distal mesoder m of the limb buds from the beginning of their outgrowth. Cyp26A1 transcrip ts are seen later and at lower levels in limb ectoderm, and both transcript s are excluded from the apical ectodermal ridge. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.