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XB-ART-35355
Dev Biol April 15, 2007; 304 (2): 786-99.

Differential ability of Ptf1a and Ptf1a-VP16 to convert stomach, duodenum and liver to pancreas.

Jarikji ZH , Vanamala S , Beck CW , Wright CV , Leach SD , Horb ME .


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.

PubMed ID: 17320068
PMC ID: PMC4868342
Article link: Dev Biol
Grant support: [+]
Genes referenced: cela1.6 gcg hhex ins pdx1 ptf1a sfrp5 sst.1 ttr
Morpholinos: ptf1a MO1 ptf1a MO2


Article Images: [+] show captions
References:
Afelik, 2006, Pubmed, Xenbase [+]


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