A retinoid-binding lipocalin, Xlcpl1, relevant for embryonic pattern formation is expressed in the nervous system of...

The importance of retinoids in early development has been increasingly recognized during the past decade. Their transport and action are mediated by extracellular, intracellular and nuclear proteins. Here we describe the isolation and characterization of a cDNA, Xlcpl1, coding for a lipocalin that is most likely involved in the transport of retinoids in the embryonic nervous system of Xenopus laevis. Lipocalins generally are carriers for small hydrophobic molecules. The expression of Xlcpl1 shows a distinct spatial and temporal pattern: transcription was observed in the anterior-most part of the neural plate at embryonic stages 13-14 whereas in adult brain, Xlcpl1 is expressed exclusively in the choroid plexus. In addition, expression was also found at the dorsal borders of the eye anlagen and in the otic vesicle of mid-neurula stage embryos. In order to gain insight into the molecular function of Xlcpl1, we caused ectopic overexpression by injecting fertilized eggs with either an excess of sense mRNA or DNA constructs under the control of the EF1α promotor. The resulting embryos developed a dysmorphogenised anterior neural system, in particular malformed heads and eyes. Phenotypic defects were therefore similar to those obtained by retinoic acid treatment at the gastrula stage or overexpression of other proteins involved in retinoic acid signalling in the early embryo. Retinoic acid treatment disrupts the endogenous gradient of retinoids that supposedly controls antero-posterior differentiation. By analogy, we propose that local overexpression of Xlcpl1 reflects precisely the situation of exogenous application of retinoic acid. In fact, we have shown biochemically that Xlcpl1 is suited to mediate the cellular retinoid signal.