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PMID:21539825

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Citation

Schmidt, M, Huber, L, Majdazari, A, Schütz, G, Williams, T and Rohrer, H (2011) The transcription factors AP-2β and AP-2α are required for survival of sympathetic progenitors and differentiated sympathetic neurons. Dev. Biol. 355:89-100

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.

Links

PubMed Online version:10.1016/j.ydbio.2011.04.011

Keywords

Animals; Cell Differentiation; Cell Survival; Cells, Cultured; Ganglia, Sensory/metabolism; Ganglia, Sympathetic/metabolism; Gene Expression Regulation, Developmental; Locus Coeruleus/metabolism; Mice; Mice, Knockout; Neural Crest/metabolism; Neural Stem Cells/metabolism; Transcription Factor AP-2/genetics; Transcription Factor AP-2/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:AP2A

acts_upstream_of_or_within

GO:0048485: sympathetic nervous system development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104672

P

  • results_in_development_of:(EMAPA:16668)

Seeded From UniProt

complete

MOUSE:AP2A

acts_upstream_of_or_within

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104672

P

  • occurs_in:(EMAPA:16881)
  • regulates_o_occurs_in:(CL:0000333)

Seeded From UniProt

complete

MOUSE:AP2B

acts_upstream_of_or_within

GO:0048485: sympathetic nervous system development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104671

P

  • results_in_development_of:(EMAPA:16668)

Seeded From UniProt

complete

MOUSE:AP2B

acts_upstream_of_or_within

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104671

P

  • occurs_in:(EMAPA:16881)
  • regulates_o_occurs_in:(CL:0000333)

Seeded From UniProt

complete


See also

References

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