Conditional ablation of Notch signaling in pancreatic development.
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.
Nakhai
Hassan
H
Department of Internal Medicine, Technical University of Munich, Ismaniger Strasse 22, 81675 Munich, Germany.
Siveke
Jens T
JT
Klein
Bettina
B
Mendoza-Torres
Lidia
L
Mazur
Pawel K
PK
Algül
Hana
H
Radtke
Freddy
F
Strobl
Lothar
L
Zimber-Strobl
Ursula
U
Schmid
Roland M
RM
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000196:embryology* / Q000502:physiology; D046790:Pancreas, Exocrine / Q000196:embryology / Q000502:physiology; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D051883:Receptor, Notch2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; C497571:Rbpj protein, mouse; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D014157:Transcription Factors; D051153:Wnt Proteins; C062602:transcription factor PTF1