Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas
Open Access
- 1 June 2008
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 22 (11), 1445-1450
- https://doi.org/10.1101/gad.1663208
Abstract
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
This publication has 34 references indexed in Scilit:
- Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complexGenes & Development, 2007
- A Multipotent Progenitor Domain Guides Pancreatic OrganogenesisDevelopmental Cell, 2007
- Epithelial Stem Cells: Turning over New LeavesCell, 2007
- Prox1 activity controls pancreas morphogenesis and participates in the production of “secondary transition” pancreatic endocrine cellsDevelopmental Biology, 2005
- Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreasDevelopment, 2004
- Evolutionary conserved role of ptf1a in the specification of exocrine pancreatic fatesDevelopmental Biology, 2004
- Gene regulatory factors in pancreatic developmentDevelopmental Dynamics, 2003
- Formation of the digestive system in zebrafish. ii. pancreas morphogenesis☆Developmental Biology, 2003
- Rat Endocrine Pancreatic Development in Relation to Two Homeobox Gene Products (Pdx-1 and Nkx 6.1)Journal of Histochemistry & Cytochemistry, 1998
- Insulin-promoter-factor 1 is required for pancreas development in miceNature, 1994