Dong P Duc Si, Provost Elayne, Leach Steven D, Stainier Didier Y R
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
Genes Dev. 2008 Jun 1;22(11):1445-50. doi: 10.1101/gad.1663208.
The mechanisms regulating pancreatic endocrine versus exocrine fate are not well defined. By analyzing the effects of Ptf1a partial loss of function, we uncovered novel roles for this transcription factor in determining pancreatic fates. In a newly identified hypomorphic ptf1a mutant, pancreatic cells that would normally express ptf1a and become exocrine cells, express the endocrine marker Isl1, indicating a cell fate switch. Surprisingly, a milder reduction of Ptf1a leads to an even greater increase of ectopic endocrine cells, suggesting that Ptf1a also plays a role in promoting endocrine development. We propose that low levels of Ptf1a promote endocrine fate, whereas high levels repress endocrine fate and promote exocrine fate.
调节胰腺内分泌与外分泌命运的机制尚未明确。通过分析Ptf1a功能部分丧失的影响，我们发现了该转录因子在决定胰腺命运方面的新作用。在一个新鉴定的低表达ptf1a突变体中，正常情况下会表达ptf1a并成为外分泌细胞的胰腺细胞，表达内分泌标志物Isl1，这表明细胞命运发生了转变。令人惊讶的是，Ptf1a水平的轻度降低会导致异位内分泌细胞的增加更为显著，这表明Ptf1a在促进内分泌发育方面也发挥了作用。我们提出，低水平的Ptf1a促进内分泌命运，而高水平则抑制内分泌命运并促进外分泌命运。
