MafA and MafB regulate genes critical to β-cells in a unique temporal manner

OBJECTIVE--Several transcription factors are essential to pancreatic islet β-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 β13-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 β-cell. RESEARCH DESIGN AND METHODS--The distribution of MafA and MafB in the β-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.sup.-/-] 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.sup.ΔPanc]). RESULTS--MafB was produced in a larger fraction of β-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.sup.ΔPunc] 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 β-cell formation and maturation. Diabetes 59:2530-2539, 2010