MafA and MafB regulate genes critical to beta-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 β-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.


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 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(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.
Artner
Isabella
I
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. isabella.artner@med.lu.se
Hang
Yan
Y
Mazur
Magdalena
M
Yamamoto
Tsunehiko
T
Guo
Min
M
Lindner
Jill
J
Magnuson
Mark A
MA
Stein
Roland
R
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005934:Glucagon / Q000096:biosynthesis; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000502:physiology*; D051473:Maf Transcription Factors, Large / Q000172:deficiency / Q000235:genetics*; D051258:MafB Transcription Factor / Q000235:genetics*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D007328:Insulin; D051473:Maf Transcription Factors, Large; D051258:MafB Transcription Factor; C485160:Mafa protein, mouse; C490406:Mafb protein, mouse; D011506:Proteins; D012333:RNA, Messenger; C502487:Rbp4 protein, mouse; D054839:Retinol-Binding Proteins, Plasma; D012313:RNA; D005934:Glucagon; D005952:Glucose-6-Phosphatase; C117983:G6pc2 protein, mouse