title: The MafA transcription factor becomes essential to islet β-cells soon after birth.
abstract: The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial-temporal patterns in rodent islet cells. Analysis of Mafa(-/-) and pancreas-specific Mafa(∆panc) deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in Mafa(Δpanc) mice and compromised earlier in Mafa(Δpanc);Mafb(+/-) mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
authors: Yan
authors: Y
authors: Hang
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
authors: Tsunehiko
authors: T
authors: Yamamoto
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
authors: Richard K P
authors: RK
authors: Benninger
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
authors: Marcela
authors: M
authors: Brissova
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
authors: Min
authors: M
authors: Guo
authors: Department of Biomedical Informatics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN.
authors: Will
authors: W
authors: Bush
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
authors: David W
authors: DW
authors: Piston
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TNDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TNVeterans Affairs Tennessee Valley Healthcare System, Nashville, TN.
authors: Alvin C
authors: AC
authors: Powers
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
authors: Mark
authors: M
authors: Magnuson
authors: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN.
authors: Debbie C
authors: DC
authors: Thurmond
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN roland.stein@vanderbilt.edu.
authors: Roland
authors: R
authors: Stein
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D007328:Insulin; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D012333:RNA, Messenger