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BIOLOGICAL SCIENCES / DEVELOPMENTAL BIOLOGY
MafB is required for islet 
cell maturation
*Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 723 Light Hall, Nashville, TN 37232; Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique–Institut National de la Santé et de la Recherche Médicale–Universite Mediterrane, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France; and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5
Communicated by Donald F. Steiner, The University of Chicago, Chicago, IL, January 2, 2007 (received for review December 6, 2006)
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 
(glucagon+) and 
(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– 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 and cells.
insulin | MafA | pancreas development
Author contributions: I.A. and R.S. designed research; I.A., B.B., J.C.R., M.G., and T.K. performed research; S.C. and M.S. contributed new reagents/analytic tools; I.A. and J.C.R. analyzed data; and I.A. and R.S. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700013104/DC1.
To whom correspondence should be addressed. E-mail: roland.stein{at}vanderbilt.edu
© 2007 by The National Academy of Sciences of the USA
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