| First Author | Nishimura W | Year | 2009 |
| Journal | Dev Biol | Volume | 333 |
| Issue | 1 | Pages | 108-20 |
| PubMed ID | 19576197 | Mgi Jnum | J:152238 |
| Mgi Id | MGI:4357715 | Doi | 10.1016/j.ydbio.2009.06.029 |
| Citation | Nishimura W, et al. (2009) Expression of MafA in pancreatic progenitors is detrimental for pancreatic development. Dev Biol 333(1):108-20 |
| abstractText | 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. |
