Cell type-specific and sexually dimorphic expression of transcription factor AP-2 in the adult mouse brain

Expression of transcription factor AP-2 family genes in adult mouse brain regions was examined at RNA and protein levels and in tissue sections. AP-2 family RNA transcripts, nuclear AP-2 DNA binding activity, and AP-2 immunoreactivity were greatest in hindbrain and midbrain regions. Cells expressing AP-2 were predominantly differentiated neurons and were abundant in the solitary tract nucleus, hypoglossal nucleus, locus coeruleus, cerebellar molecular layer, superior colliculus, mitral cell layers of the main and accessory olfactory bulbs, and in some divisions of the bed nucleus of the stria terminalis. Sexually dimorphic expression of AP-2 was seen in the bed nucleus of the stria terminalis, a forebrain region required for regulation of gender-specific reproductive and social behaviors. In males, AP-2 expressing neurons were present in supracapsular, lateral ventral, and medial ventral divisions of the bed nucleus of the stria terminalis. In contrast, females had AP-2 expressing neurons in the lateral ventral division, but not the supracapsular division, and AP-2 expression in medial ventral division neurons oscillated during the estrus cycle. With the exception of the bed nucleus of the stria terminalis, forebrain regions generally lacked cells with high levels of AP-2. However, a small population of cells co-expressing low levels of AP-2 and Notch1 was sparsely distributed in the cerebral cortex and hippocampal dentate gyrus subgranular zone. Based on their variable levels of NeuN, a marker for differentiated neurons, these cells may include nascent neurons. A subset of cerebellar Purkinje cells also co-expressed low levels of AP-2 and Notch1. Together, the adult brain regions with AP-2 expressing neurons are notable for their importance in pathways that integrate sensory and neuroendocrine information for regulation of reproductive, social, and feeding behaviors. Our data suggest that AP-2 transcription factors contribute at multiple levels to adult brain function including regulation of gender-specific behavior.