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Open Access Green as soon as Postprint is submitted to ZB.
Conditional ablation of Notch signaling in pancreatic development.
Development 135, 2757-2765 (2008)
The role of the Notch signaling members Notch1, Notch2 and Rbpj in exocrine pancreatic development is not well defined. We therefore analyzed conditional pancreas-specific Rbpj and combined Notch1/Notch2 knockout mice using Ptf1a(+/Cre(ex1)) mice crossed with floxed Rbpj or Notch1/Notch2 mice. Mice were analyzed at different embryonic stages for pancreatic exocrine and endocrine development. The absence of Rbpj in pancreatic progenitor cells impaired exocrine pancreas development up to embryonic day 18.5 and led to premature differentiation of pancreatic progenitors into endocrine cells. In Rbpj-deficient pancreata, amylase-expressing acini and islets formed during late embryonic and postnatal development, suggesting an essential role of Rbpj in early but not late development. Contrary to this severe phenotype, the concomitant inactivation of Notch1 and Notch2 only moderately disturbed the proliferation of pancreatic epithelial cells during early embryonic development, and did not inhibit pancreatic development. Our results show that, in contrast to Rbpj, Notch1 and Notch2 are not essential for pancreatogenesis. These data favor a Notch-independent role of Rbpj in the development of the exocrine pancreas. Furthermore, our findings suggest that in late stages of pancreatic development exocrine cell differentiation and maintenance are independent of Rbpj.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Notch; Rbpj; Conditional knockout mice; Pancreas; Development
Language
english
Publication Year
2008
HGF-reported in Year
2008
ISSN (print) / ISBN
0950-1991
e-ISSN
1477-9129
Quellenangaben
Volume: 135,
Issue: 16,
Pages: 2757-2765
Publisher
Company of Biologists
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501500-003
Scopus ID
52449122255
Erfassungsdatum
2008-08-29