title: The transcription factors AP-2β and AP-2α are required for survival of sympathetic progenitors and differentiated sympathetic neurons.
abstract: Differentiation of sympathetic neurons is controlled by a group of transcription factors, including Phox2b, Ascl1, Hand2 and Gata3, induced by bone morphogenetic proteins (BMPs) in progenitors located in ganglion primordia at the dorsal aorta. Here, we address the function of the transcription factors AP-2β and AP-2α, expressed in migrating neural crest cells (NCC) and maintained in sympathetic progenitors and differentiated neurons. The elimination of both AP-2α and AP-2β results in the virtually complete absence of sympathetic and sensory ganglia due to apoptotic cell death of migrating NCC. In the AP-2β knockout only sympathetic ganglia (SG) are targeted, leading to a reduction in ganglion size by about 40%, which is also caused by apoptotic death of neural crest progenitors. The conditional double knockout of AP-2α and AP-2β in sympathetic progenitors and differentiated noradrenergic neurons results in a further decrease in neuron number, leading eventually to small sympathetic ganglion rudiments postnatally. The elimination of AP-2β also leads to the complete absence of noradrenergic neurons of the Locus coeruleus (LC). Whereas AP-2α/β transcription factors are in vivo not required for the onset or maintenance of noradrenergic differentiation, their essential survival functions are demonstrated for sympathetic progenitors and noradrenergic neurons.
authors.affiliation: Research Group Developmental Neurobiology, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, Frankfurt/M, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Schmidt
authors.forename: Leslie
authors.initials: L
authors.lastname: Huber
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Majdazari
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
authors.forename: Trevor
authors.initials: T
authors.lastname: Williams
authors.forename: Hermann
authors.initials: H
authors.lastname: Rohrer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D017950:Ganglia, Sensory / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008125:Locus Coeruleus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050656:Transcription Factor AP-2