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First published online 17 July 2008
doi: 10.1242/dev.013722
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1 Department of Internal Medicine, Technical University of Munich, Ismaniger
Strasse 22, 81675 Munich, Germany.
2 Institute of Immunology, Friedrich-Loeffler Institut, Paul-Ehrlich Strasse 28,
72076 Tuebingen, Germany.
3 ISREC, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
4 GSF-National Research Center for Environment and Health, Institute for
Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, 81377
Munich, Germany.
Author for correspondence (e-mail:
roland.schmid{at}lrz.tum.de)
Accepted 17 June 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.
Key words: Notch, Rbpj, Conditional knockout mice, Pancreas, Development
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