Metabolism to a response pathway selective retinoid ligand during axial pattern formation

We report identification of 9-cis-4-oxo-retinoic acid (9-cis-4-oxo-RA) as a n in vivo retinoid metabolite in Xenopus embryos. 9-Cis-4-oxo-RA bound rece ptors (RARs) alpha; beta, and gamma as well as retinoid X receptors (RXRs) alpha, beta, and gamma in vitro. However, this retinoid displayed different ial RXR activation depending on the response pathway used. Although it fail ed to activate RXRs in RXR homodimers, it activated RXRs and RARs synergist ically in RAR-RXR heterodimers. 9-Cis-4-oxo-RA thus acted as a dimer-specif ic agonist. Considering that RAR-RXR heterodimers are major functional unit s involved in transducing retinoid signals during embryogenesis and that 9- cis-3-oxo-RA displayed high potency for modulating axial pattern formation in Xenopus, metabolism to 9-cis-4-oxo-RA may provide a mechanism to target retinoid action to this and other RAR-RXR heterodimer-mediated processes.