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MafA and MafB Regulate Genes Critical to beta-Cells in a Unique Temporal Manner

Artner, Isabella LU ; Hang, Yan; Mazur, Magdalena LU ; Yamamoto, Tsunehiko; Guo, Min; Lindner, Jill; Magnuson, Mark A. and Stein, Roland (2010) In Diabetes 59(10). p.2530-2539
Abstract
OBJECTIVE-Several transcription factors are essential to pancreatic islet beta-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with beta-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the beta-cell. RESEARCH DESIGN AND METHODS-The distribution of MafA and MafB in the beta-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(-/-)... (More)
OBJECTIVE-Several transcription factors are essential to pancreatic islet beta-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with beta-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the beta-cell. RESEARCH DESIGN AND METHODS-The distribution of MafA and MafB in the beta-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(-/-) pancreata at embryonic day 18.5, with candidates evaluated by quantitative RT-PCR and in situ hybridization. The potential role of MafA in the expression of verified targets was next analyzed in adult islets of a pancreas-wide MafA mutant (termed MafA(Delta Panc)). RESULTS-MafB was produced in a larger fraction of beta-cells than MafA during development and found to regulate potential effectors of glucose sensing, hormone processing, vesicle formation, and insulin secretion. Notably, expression from many of these genes was compromised in MafA(Delta Panc) islets, suggesting that MafA is required to sustain expression in adults. CONCLUSIONS-Our results provide insight into the sequential manner by which MafA and MafB regulate islet beta-cell formation and maturation. Diabetes 59:2530-2539, 2010 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
59
issue
10
pages
2530 - 2539
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000283205700026
  • scopus:77957583357
ISSN
1939-327X
DOI
10.2337/db10-0190
language
English
LU publication?
yes
id
5956afb0-3122-45c0-a416-3aa52a0a5cc6 (old id 1720959)
date added to LUP
2010-12-03 13:06:28
date last changed
2018-05-29 11:55:03
@article{5956afb0-3122-45c0-a416-3aa52a0a5cc6,
  abstract     = {OBJECTIVE-Several transcription factors are essential to pancreatic islet beta-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with beta-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the beta-cell. RESEARCH DESIGN AND METHODS-The distribution of MafA and MafB in the beta-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(-/-) pancreata at embryonic day 18.5, with candidates evaluated by quantitative RT-PCR and in situ hybridization. The potential role of MafA in the expression of verified targets was next analyzed in adult islets of a pancreas-wide MafA mutant (termed MafA(Delta Panc)). RESULTS-MafB was produced in a larger fraction of beta-cells than MafA during development and found to regulate potential effectors of glucose sensing, hormone processing, vesicle formation, and insulin secretion. Notably, expression from many of these genes was compromised in MafA(Delta Panc) islets, suggesting that MafA is required to sustain expression in adults. CONCLUSIONS-Our results provide insight into the sequential manner by which MafA and MafB regulate islet beta-cell formation and maturation. Diabetes 59:2530-2539, 2010},
  author       = {Artner, Isabella and Hang, Yan and Mazur, Magdalena and Yamamoto, Tsunehiko and Guo, Min and Lindner, Jill and Magnuson, Mark A. and Stein, Roland},
  issn         = {1939-327X},
  language     = {eng},
  number       = {10},
  pages        = {2530--2539},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {MafA and MafB Regulate Genes Critical to beta-Cells in a Unique Temporal Manner},
  url          = {http://dx.doi.org/10.2337/db10-0190},
  volume       = {59},
  year         = {2010},
}