title: MafB is required for islet beta cell maturation.
abstract: Pancreatic endocrine cell differentiation depends on transcription factors that also contribute in adult insulin and glucagon gene expression. Islet cell development was examined in mice lacking MafB, a transcription factor expressed in immature alpha (glucagon(+)) and beta (insulin(+)) cells and capable of activating insulin and glucagon expression in vitro. We observed that MafB(-/-) embryos had reduced numbers of insulin(+) and glucagon(+) cells throughout development, whereas the total number of endocrine cells was unchanged. Moreover, production of insulin(+) cells was delayed until embryonic day (E) 13.5 in mutant mice and coincided with the onset of MafA expression, a MafB-related activator of insulin transcription. MafA expression was only detected in the insulin(+) cell population in MafB mutants, whereas many important regulatory proteins continued to be expressed in insulin(-) beta cells. However, Pdx1, Nkx6.1, and GLUT2 were selectively lost in these insulin-deficient cells between E15.5 and E18.5. MafB appears to directly regulate transcription of these genes, because binding was observed within endogenous control region sequences. These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 723 Light Hall, Nashville, TN 37232, USA.
authors.forename: Isabella
authors.initials: I
authors.lastname: Artner
authors.forename: Bruno
authors.initials: B
authors.lastname: Blanchi
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Raum
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Sabine
authors.initials: S
authors.lastname: Cordes
authors.forename: Michael
authors.initials: M
authors.lastname: Sieweke
authors.forename: Roland
authors.initials: R
authors.lastname: Stein
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005934:Glucagon / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; C491328:Nkx6-1 protein, mouse; C495682:Slc2a2 protein, mouse; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005934:Glucagon