Cell type-specific regulation of expression of transcription factor AP-2 in neuroectodermal cells.
AP-2 is a cell type-specific DNA-binding transcription factor that regulates selected target genes in vertebrate organisms. Here we investigated cell type-specific expression and regulation of 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 strong induction 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 astrocytes to express AP-2 was ascertained by using cerebellar neurons and astrocytes derived from newborn mice. Unlike these types of cells, 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 by inhibitors of protein kinase A. In contrast to its action in P19 cells, RA had no effect on AP-2 mRNA levels in primary astrocytes. Our results indicate that AP-2 may play a role as a retinoic acid-sensitive regulator during differentiation of neurons and glia from an embryonic neural precursor. Furthermore, AP-2 may be involved in gene transcription in both mature neurons and astrocytes.
University Hospital of Zurich, Department of Internal Medicine, Switzerland.
J
J
Philipp
P J
PJ
Mitchell
U
U
Malipiero
A
A
Fontana
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D002531:Cerebellum / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004475:Ectoderm / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000235:genetics; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D017931:DNA Primers; D004268:DNA-Binding Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D014212:Tretinoin; D003994:Bucladesine; D000242:Cyclic AMP