Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas.
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.
Dong
P Duc Si
PD
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA. didier-stainier@biochem.ucsf.edu
Provost
Elayne
E
Leach
Steven D
SD
Stainier
Didier Y R
DY
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D007515:Islets of Langerhans / Q000196:embryology*; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D014157:Transcription Factors; D029961:Zebrafish Proteins; C062602:transcription factor PTF1