ORPHAN RECEPTOR COUP-TF-I ANTAGONIZES RETINOIC ACID-INDUCED NEURONAL DIFFERENTIATION

Chicken ovalbumin upstream promoter-transcription factors (COUP-TF) ar e expressed in the developing nervous system and interact with nuclear hormone receptors to regulate expression of different genes. The role of COUP-TF orphan receptors in neurogenesis is virtually unknown, To study the possible function of COUP-TF I during neuronal differentiati on, we generated COUP-TF I overexpressing teratocarcinoma PCC7 cell li nes and analyzed retinoic acid (RA)-induced neuronal differentiation o f these cells, COUP-TF I overexpression results in the blockade of mor phological differentiation after induction to differentiate. COUP-TF I represses expression of microtubule-associated protein 2 (MAP2) gene and delays induction of growth-associated protein 43 (GAP43) gene expr ession, In contrast, expression of the neurofilament light subunit (NF -L) gene is not affected by COUP-TF I overexpression during neuronal d ifferentiation. Also, cells overexpressing COUP-TF I do not stop proli ferating after RA and dBcAMP treatment and possess suppressed transcri ptional activation from different RA response elements, These results suggest that COUP-TF I plays an important role in regulating RA-induce d neuronal differentiation. (C) 1995 Wiley-Liss, Inc.