Orphan receptor COUP‐TF I antagonizes retinoic acid‐induced neuronal differentiation

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Abstract
Chicken ovalbumin upstream promoter‐transcription factors (COUP‐TF) are 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 differentiation, we generated COUP‐TF I overexpressing teratocarcinoma PCC7 cell lines and analyzed retinoic acid (RA)‐induced neuronal differentiation of these cells. COUP‐TF I overexpression results in the blockade of morphological differentiation after induction to differentiate. COUP‐TF I represses expression of micro‐tubule‐associated protein 2 (MAP2) gene and delays induction of growth‐associated protein 43 (GAP43) gene expression. In contrast, expression of the neurofilament light subunit (NF‐L) gene is not affected by COUP‐TF I overexpression during neuronal differentiation. Also, cells overexpressing COUP‐TF I do not stop proliferating after RA and dBcAMP treatment and possess suppressed transcriptional activation from different RA response elements. These results suggest that COUP‐TF I plays an important role in regulating RA‐induced neuronal differentiation.