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Keywords:

  • dopamine;
  • retinoic acid;
  • RXR;
  • striatum

Abstract

Dopamine and adenosine 3′:5′-monophosphate-regulated phosphoprotein (DARPP-32) is a key molecule for dopamine neurotransmission. The molecular mechanisms underlying the regulation of DARPP-32 in the developing brain remains elusive. Previous studies have shown that retinoids are capable of inducing DARPP-32 in striatal cell culture, suggesting that retinoids are candidate molecules for controlling DARPP-32 expression. In the present study, we first studied the expression profiles of retinoid receptors and their associated co-factors in the developing rat telencephalon by RT-PCR. The results showed that among the retinoid receptors, RARβ and RXRγ were nearly selectively expressed in the developing striatum. By contrast, the retinoid receptors associated transcriptional co-factors, including the co-repressors of N-CoR and SMRT, and the co-activators of SRC-1 and P/CAF, were ubiquitously expressed in the developing telencephalon. In light of the previous findings that DARPP-32 was inducible by retinoids in striatal culture, but not in cortical culture, we hypothesized that the striatum-selective RARβ and RXRγ may mediate DARPP-32 induction by retinoids. To test this hypothesis, we used the gain-of-function approach to ectopically express RARβ and RXRγ in the developing cerebral cortex that lacked these two retinoid receptors. Ectopic expression of RARβ1, but not RXRγ1, up-regulated DARPP-32 in the cortical explant culture. Notably, DARPP-32 was up-regulated only by the RARβ1 isoform, but not by other RARβ isoforms. Our study suggests that RARβ signaling may regulate DARPP-32 gene expression by an isoform-specific mechanism in developing telencephalic neurons. The molecular diversity of RARβ isoforms may underlie parts of the complex gene regulation by retinoids during neural development.