title: Transcription factor AP-2β regulates the neurotransmitter phenotype and maturation of chromaffin cells.
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.
authors.affiliation: Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. seok-hong@northwestern.edu
authors.forename: Seok Jong
authors.initials: SJ
authors.lastname: Hong
authors.forename: Yang Hoon
authors.initials: YH
authors.lastname: Huh
authors.forename: Amanda
authors.initials: A
authors.lastname: Leung
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Yunmin
authors.initials: Y
authors.lastname: Ding
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Kang
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Yoo
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism; D000320:Adrenergic Fibers / Q000378:metabolism; D000818:Animals; D019439:Chromaffin Cells / Q000166:cytology / Q000502:physiology*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010641:Phenotype; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D022142:Secretory Vesicles / Q000648:ultrastructure; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D050656:Transcription Factor AP-2; D014446:Tyrosine 3-Monooxygenase; D010625:Phenylethanolamine N-Methyltransferase; D009638:Norepinephrine; D004837:Epinephrine