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

Abstract 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 regards to temporal and islet cell expression pattern, with β cells only affected by MafB 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 −/− pancreata at embryonic day 18.5, with candidates evaluated by qRT-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 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 ΔPanc 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.