QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 17 July 2008
doi: 10.1242/dev.013722

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.013722v1 135/16/2757    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Nakhai, H. Articles by Schmid, R. M. PubMed PubMed Citation Articles by Nakhai, H. Articles by Schmid, R. M.

Conditional ablation of Notch signaling in pancreatic development

Hassan Nakhai^1,*, Jens T. Siveke^1,*, Bettina Klein², Lidia Mendoza-Torres¹, Pawel K. Mazur¹, Hana Algül¹, Freddy Radtke³, Lothar Strobl⁴, Ursula Zimber-Strobl⁴ and Roland M. Schmid^1,

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

This article has been cited by other articles:

				K. S. Zaret and M. Grompe Generation and Regeneration of Cells of the Liver and Pancreas Science, December 5, 2008; 322(5907): 1490 - 1494. [Abstract] [Full Text] [PDF]

				H. Nakhai, J. T. Siveke, L. Mendoza-Torres, and R. M. Schmid Conditional inactivation of Myc impairs development of the exocrine pancreas Development, October 1, 2008; 135(19): 3191 - 3196. [Abstract] [Full Text] [PDF]