References
Query Results -- Details
MGI Accession ID: MGI:4357715
J Number: J:152238
Other Accession IDs:
Title: Expression of MafA in pancreatic progenitors is detrimental for pancreatic development.
Authors: Nishimura W; Bonner-Weir S; Sharma A
Journal: Dev Biol
Volume: 333
Issue: 1
Date: 2009 Sep 1
Year: 2009
Pages: 108-20
Review Status: Peer Reviewed
Abstract:
The transcription factor MafA regulates glucose-responsive expression of insulin. MafA-deficient mice have a normal proportion of insulin+ cells at birth but develop diabetes gradually with age, suggesting that MafA is required for maturation and not specification of pancreatic beta-cells. However, several studies show that ectopic expression of MafA may have a role in specification as it induces insulin+ cells in chicken gut epithelium, reprograms adult murine acinar cells into insulin+ cells in combination with Ngn3 and Pdx1, and triggers the lens differentiation. Hence, we examined whether MafA can induce specification of beta-cells during pancreatic development. When the MafA transgene is expressed in Pdx1+ pancreatic progenitors, both pancreatic mass and proliferation of progenitors are reduced, at least partially due to induction of cyclin kinase inhibitors p27 and p57. Expression of MafA in Pdx1+ cells until E12.5 was sufficient to cause these effects and to disproportionately inhibit the formation of endocrine cells in the remnant pancreas. Thus, in mice, MafA expression in Pdx1+ pancreatic progenitors is not sufficient to specify insulin+ cells but in fact deters pancreatic development and the differentiation of endocrine cells. These findings imply that MafA should be used to enhance maturation, rather than specification, of beta-cells from stem/progenitor cells.
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