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

Dev Biol. 1994 Oct;165(2):602-14. doi: 10.1006/dbio.1994.1279.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / metabolism*
  • Base Sequence
  • Bucladesine / pharmacology
  • Cell Differentiation
  • Cerebellum / metabolism*
  • Cyclic AMP / physiology
  • DNA Primers / chemistry
  • DNA-Binding Proteins / metabolism*
  • Ectoderm / metabolism*
  • Gene Expression / drug effects
  • Mice
  • Microglia / metabolism*
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Protein Kinase Inhibitors
  • RNA, Messenger / genetics
  • Transcription Factor AP-2
  • Transcription Factors / metabolism*
  • Tretinoin / pharmacology


  • DNA Primers
  • DNA-Binding Proteins
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Transcription Factor AP-2
  • Transcription Factors
  • Tretinoin
  • Bucladesine
  • Cyclic AMP