Cell type-specific regulation of expression of transcription factor AP-2 in neuroectodermal cells

AP-2 is a cell type-specific DNA-bindingtranscription factor that regulates selected targetgenes in vertebrate organisms. Here we investigated cell type-specific expression and regulationof AP-2 in neuroectodermal cell lineages. During retinoic acid (RA)-mediated differentiation of P19 embryonal carcinoma cells into neuroectodermal cell types that include immunohistochemically defined neurons and astrocytes, we observed a stronginduction of AP-2 transcripts and protein. In contrast, AP-2 mRNA was not induced in P19 cells which undergo mesoendodermal differentiation in response to 1% dimethylsulfoxide or low concentrations of RA, respectively. The potential of both neurons and astrocytesto express AP-2 wasascertained by using cerebellar neurons and astrocytes derived from newborn mice. Unlike these types ofcells, microglial cells do not express AP-2. Dibutyryl cyclic AMP further enhanced levels of AP-2 transcripts in both P19 astrocytes and primary astrocytes which also respond to agents elevating intracellular cAMP (noradrenaline, isoproterenol, forskolin). The cAMP-dependent induction of AP-2 could be blocked byinhibitors of protein kinase A. In contrast to its action in P19 cells, RA had no effect on AP-2 mRNA levels in primary astrocytes. Ourresults indicate that AP-2 may playa role as a retinoic acid-sensitive regulator during differentiation of neurons and gliafrom an embryonic neuralprecursor. Furthermore, AP-2 may be involved in gene transcription in both mature neuronsand astrocytes.