TY - JOUR
T1 - Transcription factor AP-2β regulates the neurotransmitter phenotype and maturation of chromaffin cells
AU - Hong, Seok Jong
AU - Huh, Yang Hoon
AU - Leung, Amanda
AU - Choi, Hyun Jin
AU - Ding, Yunmin
AU - Kang, Un Jung
AU - Yoo, Seung Hyun
AU - Buettner, Reinhard
AU - Kim, Kwang Soo
N1 - Funding Information:
We would like to thank Betty Eipper for the DBH antibody and Matthew Geringer for his critical review of the manuscript. This work was supported by NIH grants ( MH48866 and MH087903 ).
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - AP-2β
KW - Chromaffin cells
KW - Chromatin immunoprecipitation (ChIP) assays
KW - Epinephrine
KW - Large secretory vesicles
KW - Phenylethanolamine-N-methyl-transferase
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U2 - 10.1016/j.mcn.2010.09.007
DO - 10.1016/j.mcn.2010.09.007
M3 - Article
C2 - 20875861
AN - SCOPUS:78650858770
VL - 46
SP - 245
EP - 251
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
SN - 1044-7431
IS - 1
ER -