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GENES & DEVELOPMENT 22:1445-1450, 2008
©2008 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH COMMUNICATION

Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas

P. Duc Si Dong1,4, Elayne Provost2, Steven D. Leach2, and Didier Y.R. Stainier1,3

1 Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA; 2 Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA

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.

[Keywords: Ptf1a; diabetes; endocrine; exocrine; pancreas]

Received February 14, 2008; revised version accepted April 4, 2008.

3 Corresponding authors.

E-MAIL didier_stainier{at}biochem.ucsf.edu; FAX (415) 476-3892.

4 E-MAIL duc.dong{at}ucsf.edu; FAX (415) 476-3892.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1663208.


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