AN EVOLUTIONARY CONSERVED COUP-TF BINDING-ELEMENT IN A NEURAL-SPECIFIC GENE AND COUP-TF EXPRESSION PATTERNS SUPPORT A MAJOR ROLE FOR COUP-TF IN NEURAL DEVELOPMENT

The COUP transcription factors (COUP-TF and ARP-1) are the most highly conserved members of the nuclear receptor superfamily throughout evol ution. Previous studies indicated that COUP orphan receptors may be in volved in early neurogenesis in Drosophila and zebrafish. Here we iden tified a neural-specific gene, arrestin, whose transcription can be re gulated by endogenous COUPs through a DR-7 element (direct repeat with a 7-base pair spacer) located upstream of the transcription start sit e. Importantly, the COUP binding site of the arrestin gene promoter is conserved among mouse, bovine, and human. However, the mouse element is also capable of responding to retinoic acid while the element in th e human gene does not. Expression of COUP-TF correlates with the known expression sites of the arrestin gene in vivo, notably during the dif ferentiation of the retina. We also show that COUP-TF is expressed in a spatio-temporally defined pattern in the murine central nervous syst em during embryogenesis. It appears that the expression pattern of COU P-TF is unique in certain regions of the developing brain, which would indicate a novel role for COUP-TF and/or ARP-1, distinct from their r ole in restricting other hormonal signaling pathways. Together our dat a suggest that COUPs play a crucial role in controlling a subset of ne ural-specific programs during development.