Abstract
Determining the functional attributes of pancreatic transcription factors is essential to understand how the pancreas is specified distinct from other endodermal organs, such as liver, stomach and duodenum, and to direct the differentiation of other cell types into pancreas. Previously, we demonstrated that Pdx1-VP16 was sufficient to convert liver to pancreas. In this paper, we characterize the functional ability of another pancreatic transcription factor, Ptf1a, in promoting ectopic pancreatic fates at early stages throughout the endoderm and later during organogenesis. Using the transthyretin promoter to drive expression in the early liver region/bud of transgenic Xenopus tadpoles, we find that Ptf1a-VP16 is able to convert liver to pancreas. Overexpression of the unmodified Ptf1a on the other hand has no effect in liver but is able to convert stomach and duodenum to pancreas. When overexpressed at earlier embryonic stages throughout the endoderm, Ptf1a activity is similarly limited, whereas Ptf1a-VP16 has increased activity. Interestingly, in all instances we find that Ptf1a-VP16 is only capable of promoting acinar cell fates, whereas Ptf1a promotes both acinar and endocrine fates. Lastly, we demonstrate that, similar to mouse and zebrafish, Xenopus Ptf1a is essential for the initial specification of both endocrine and exocrine cells during normal pancreas development.
Original language | English (US) |
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Pages (from-to) | 786-799 |
Number of pages | 14 |
Journal | Developmental biology |
Volume | 304 |
Issue number | 2 |
DOIs | |
State | Published - Apr 15 2007 |
Externally published | Yes |
Keywords
- Endocrine
- Exocrine
- Organogenesis
- Pancreas
- Ptf1a
- Specification
- Transdifferentiation
- Xenopus
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology