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Regulation of the noradrenaline neurotransmitter phenotype by the transcription factor AP-2beta.

Authors
  • Hong, Seok Jong
  • Lardaro, Thomas
  • Oh, Myung Sook
  • Huh, Youngbuhm
  • Ding, Yunmin
  • Kang, Un Jung
  • Kirfel, Jutta
  • Buettner, Reinhard
  • Kim, Kwang-Soo
Type
Published Article
Journal
The Journal of biological chemistry
Publication Date
Jun 13, 2008
Volume
283
Issue
24
Pages
16860–16867
Identifiers
DOI: 10.1074/jbc.M709106200
PMID: 18424435
Source
Medline
License
Unknown

Abstract

AP-2 family transcription factors are essential for development and morphogenesis of diverse tissues and organs, but their precise roles in specification of neural crest stem cell (NCSC)-derived cell types have not been determined. Among three members known to be expressed in the NCSC (i.e. AP-2alpha, AP-2beta, and AP-2gamma), we found that only AP-2beta is predominantly expressed in the sympathetic ganglia of developing mouse embryos, supporting its role in sympathetic development. Indeed, AP-2beta null mice expressed significantly reduced levels of both noradrenaline (NA) and NA-synthesizing dopamine beta-hydroxylase in the peripheral nervous system. Strikingly, we also found that NA neuron development was significantly compromised in the locus coeruleus as well. Pharmacological treatment with an NA intermediate during pregnancy significantly rescues the neonatal lethality of AP-2beta(-/-) mice, indicating that NA deficiency is one of the main causes for lethality found in AP-2beta(-/-) mice. We also showed that forced expression of AP-2beta, but not other AP-2 factors, in NCSC favors their differentiation into NA neurons. In summary, we propose that AP-2beta plays critical and distinctive roles in the NA phenotype specification in both the peripheral and central nervous system during development.

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