title: A subtractive gene expression screen suggests a role of transcription factor AP-2 alpha in control of proliferation and differentiation.
abstract: The transcription factor AP-2 alpha has been implicated as a cell type-specific regulator of gene expression during vertebrate embryogenesis based on its expression pattern in neural crest cells, ectoderm, and the nervous system in mouse and frog embryos. AP-2 alpha is prominently expressed in cranial neural crest cells, a population of cells that migrate from the lateral margins of the brain plate during closure of the neural tube at day 8-9 of embryonic development. Homozygous AP-2 alpha mutant mice die perinatally with cranio-abdominoschisis, full facial clefting, and defects in cranial ganglia and sensory organs, indicating the importance of this gene for proper development. By using a subtractive cloning approach, we identified a set of genes repressed by AP-2 alpha that are described to retard cellular proliferation and induce differentiation and apoptosis. We show that these target genes are prematurely expressed in AP-2 alpha mutant mice. One of the genes isolated, the Krüppel-box transcription factor KLF-4 implicated in induction of terminal differentiation and growth regulation, is found expressed in mutant embryonic fibroblasts. We show that fibroblasts lacking AP-2 alpha display retarded growth but no enhanced apoptosis. Based on these data we suggest that AP-2 alpha might be required for cell proliferation by suppression of genes inducing terminal differentiation, apoptosis, and growth retardation.
authors.affiliation: Forschungszentrum Karlsruhe, ITG, Hermann von Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Pfisterer
authors.forename: Julia
authors.initials: J
authors.lastname: Ehlermann
authors.forename: Martin
authors.initials: M
authors.lastname: Hegen
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D051379:Mice; D009420:Nervous System / Q000196:embryology; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D011898:Ranidae; D012097:Repressor Proteins / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011506:Proteins; D012097:Repressor Proteins; C493668:Tfap2a protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors