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MafB is required for islet beta cell maturation

Artner, Isabella LU ; Blanchi, Bruno; Raum, Jeffrey C; Guo, Min; Kaneko, Tomomi; Cordes, Sabine; Sieweke, Michael and Stein, Roland (2007) In Proceedings of the National Academy of Sciences of the United States of America 104(10). p.8-3853
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... (More)

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.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Animals, Cell Differentiation, Glucagon, Glucose Transporter Type 2, Homeodomain Proteins, Insulin, Insulin-Secreting Cells, MafB Transcription Factor, Mice, Mice, Transgenic, Models, Biological, Mutation, Time Factors, Trans-Activators, Transcription, Genetic
in
Proceedings of the National Academy of Sciences of the United States of America
volume
104
issue
10
pages
6 pages
publisher
National Acad Sciences
external identifiers
  • scopus:34247183601
ISSN
0027-8424
DOI
10.1073/pnas.0700013104
language
English
LU publication?
no
id
1c124521-0cec-4d39-b1c4-43d39bb15169
date added to LUP
2017-06-13 12:50:03
date last changed
2017-10-29 05:02:34
@article{1c124521-0cec-4d39-b1c4-43d39bb15169,
  abstract     = {<p>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.</p>},
  author       = {Artner, Isabella and Blanchi, Bruno and Raum, Jeffrey C and Guo, Min and Kaneko, Tomomi and Cordes, Sabine and Sieweke, Michael and Stein, Roland},
  issn         = {0027-8424},
  keyword      = {Animals,Cell Differentiation,Glucagon,Glucose Transporter Type 2,Homeodomain Proteins,Insulin,Insulin-Secreting Cells,MafB Transcription Factor,Mice,Mice, Transgenic,Models, Biological,Mutation,Time Factors,Trans-Activators,Transcription, Genetic},
  language     = {eng},
  month        = {03},
  number       = {10},
  pages        = {8--3853},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {MafB is required for islet beta cell maturation},
  url          = {http://dx.doi.org/10.1073/pnas.0700013104},
  volume       = {104},
  year         = {2007},
}