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

Research output: Contribution to journalArticle

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

Details

Authors
  • Isabella Artner
  • Yan Hang
  • Magdalena Mazur
  • Tsunehiko Yamamoto
  • Min Guo
  • Jill Lindner
  • Mark A. Magnuson
  • Roland Stein
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)2530-2539
JournalDiabetes
Volume59
Issue number10
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell and Pancreas Developmental Biology (013212044)

Related research output

Mazur, M., 2013, Stem Cell Center, Lund University. 144 p.

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