The expression of retinoic acid receptors in Xenopus development.

Abstract

--Transport Interaction with the nucleus other pathways, ---Binding t o e.g. THR. VitDR receptors COUPS Introduction Ketinoic acid (KA) is a derivative of vitamin A that has profound effects on the development of vertebrate embryos [1,2]. This is clearly seen when exogenous RA is added to embryos as it causes reproducible defects in anterior-posterior (AP) axis formation and craniofacial development [ 1,2]. Morphological defects are accompanied by alterations in the patterns of expression of developmentally significant genes such as those of the HOX family [ 3,4]. Importantly, although there is still some debate about the active form, RA has been found in a range of embryos at relevant developmental stages [ 5-71. These observations have led to the idea that KA may be an endogenous signalling rnolecule. RA is a small, highly hydrophobic molecule. I;rom synthesis onwards it is probably associated with a series of specific proteins. Figure 1 illustrates the signalling pathway of RA from synthesis to gene expression. It is clear that there are many points at which this pathway may be controlled and where diversity of response t o KA can be generated. Transport proteins are responsible for delivery of retinoids t o cells [CU]. Within the cell the cellular RAbinding proteins (CRAHPs) may regulate the metabolism of M, the amount of free RA and its transport to the nucleus [9]. Following this complicated supply route, which may include several regulatory steps, RA in the nucleus binds to proteins that are members of the steroid hormone receptor superfamily [lo]. RA receptors are ligand-modulated transcription factors and represent the effector proteins of the RA signalling pathway. I here are two classes of receptor, termed KAK and RXK [ 10.1 11. Within each class there are three genes termed a, /3 and y. The sequences of KAKs a, /? and y are more closely related to each other than to the RXR genes. The RXRs are related to the Drosophila protein ultraspiracle. In cell culture, both ultraspiracle and KXR, but not RAR, can heterodimerize with the Drosophilu ecdysone receptor, resulting in promoter binding and tran7 ,