Transcription factor AP-2β regulates the neurotransmitter phenotype and maturation of chromaffin cells

Seok Jong Hong*, Yang Hoon Huh, Amanda Leung, Hyun Jin Choi, Yunmin Ding, Un Jung Kang, Seung Hyun Yoo, Reinhard Buettner, Kwang Soo Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

During development, sympathetic neurons and chromaffin cells originate from bipotential sympathoadrenal (SA) progenitors arising from neural crests (NC) in the trunk regions. Recently, we showed that AP-2β, a member of the AP2 family, plays a critical role in the development of sympathetic neurons and locus coeruleus and their norepinephrine (NE) neurotransmitter phenotype. In the present study, we investigated the potential role of AP-2β in the development of NC-derived neuroendocrine chromaffin cells of the adrenal medulla and the epinephrine (EPI) phenotype determination. In support of its role in chromaffin cell development, AP-2β is prominently expressed in both embryonic and adult adrenal medulla. In adrenal chromaffin cells of the AP-2β-/- mouse, the expression levels of catecholamine biosynthesizing enzymes, dopamine β-hydroxylase (DBH) and phenylethanolamine-N-methyl-transferase (PNMT), as well as the SA-specific transcription factor, Phox2b, are significantly reduced compared to wild type. In addition, ultrastructural analysis demonstrated that the formation of large secretory vesicles, a hallmark of differentiated chromaffin cells, is defective in AP-2β-/- mice. Furthermore, the level of EPI content is largely diminished (>80%) in the adrenal gland of AP-2β-/- mice. Chromatin immunoprecipitation (ChIP) assays of rat adrenal gland showed that AP-2β binds to the upstream promoter of the PNMT gene in vivo; strongly suggesting that it is a direct target gene. Overall, our data suggest that AP-2β plays critical roles in the epinephrine phenotype and maturation of adrenal chromaffin cells.

Original languageEnglish (US)
Pages (from-to)245-251
Number of pages7
JournalMolecular and Cellular Neuroscience
Volume46
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • AP-2β
  • Chromaffin cells
  • Chromatin immunoprecipitation (ChIP) assays
  • Epinephrine
  • Large secretory vesicles
  • Phenylethanolamine-N-methyl-transferase

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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