RARbeta isoform-specific regulation of DARPP-32 gene expression: an ectopic expression study in the developing rat telencephalon.
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, RARbeta and RXRgamma 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 RARbeta and RXRgamma may mediate DARPP-32 induction by retinoids. To test this hypothesis, we used the gain-of-function approach to ectopically express RARbeta and RXRgamma in the developing cerebral cortex that lacked these two retinoid receptors. Ectopic expression of RARbeta1, but not RXRgamma1, up-regulated DARPP-32 in the cortical explant culture. Notably, DARPP-32 was up-regulated only by the RARbeta1 isoform, but not by other RARbeta isoforms. Our study suggests that RARbeta signaling may regulate DARPP-32 gene expression by an isoform-specific mechanism in developing telencephalic neurons. The molecular diversity of RARbeta isoforms may underlie parts of the complex gene regulation by retinoids during neural development.
Liao
Wen-Lin
WL
Institute of Neuroscience, National Yang-Ming University, 155 Li-Rum Street, Taipei 11211, Taiwan.
Liu
Fu-Chin
FC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D049230:Retinoid X Receptor beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism*; D014162:Transfection / Q000379:methods
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D049230:Retinoid X Receptor beta